FIELD OF INVENTION
The present invention relates to novel polyphenolic boron adducts, their synthesis and uses thereof, covering anticancer activity.
BACKGROUND AND PRIOR ART
Cancer is a group of diseases involving uncontrolled proliferation of cells and complications arising thereby, thus, being the second most fatal disease globally. According to GLOBOCAN, about 18.1 million new cancer cases and 9.6 million deaths have been reported worldwide, in the year 2018. The projected cancer burden in India was about 26.7 million new cases in the year 2021. [Kulothungan V, Sathishkumar K, Leburu S, Ramamoorthy T, Stephen S, Basavarajappa D, Tomy N, Mohan R, Menon GR, Mathur P. Burden of cancers in India-estimates of cancer crude incidence, YLLs, YLDs and DALYs for 2021 and 2025 based on National Cancer Registry Program. BMC cancer. 2022 May 11;22(1):527.]. Treatment of cancer includes various strategies, such as chemotherapy, radiotherapy, immunotherapy and surgery, out of which, chemotherapy goes with the patient right from the onset of the disease, and comprises of drug therapy as well as natural remedies.
Boron has been gradually resurfacing for its medical importance after several studies proved its nutrient value as well as its medicinal properties. For decades, boron-containing compounds were used as antiseptics, thus gaining significance for external usage. However, recent studies proved that Boron compounds can also be used as internal agents. The recently FDA-approved drug Bortezomib successfully cemented the metal's biological activity and nullified its toxicity concerns. Boron is a micronutrient present in the animal body with an indispensable function, playing a vital role in various processes including the folding of macrolides inside the human body, maintenance of Vitamin D levels, and improving bone health as well as combating the cancer risk in mammalian cells. Moreover, it was found to be appropriately stable in the physiological pH, helping the element to attain a huge pharmaceutical applicability. Boron has served as a therapeutic agent for various diseases including cancer, HIV, rheumatoid arthritis, bacterial infections, and fungal infections. Therefore, boron chemistry attained huge momentum resulting in the design and development of a new range of medicinal compounds [Chatterjee S, Tripathi NM, Bandyopadhyay A. The modern role of boron as a ‘magic element’in biomedical science: chemistry perspective. Chemical Communications. 2021;57(100):13629-40.]
Use of polyphenolic compounds such as quercetin is well established as an assitive remedy during cancer treatment. Possessing antioxidant properties, quercetin activates the Reactive Oxygen Species in human body, leading to its anticancer effect [Ezzati M, Yousefi B, Velaei K, Safa A. A review on anti-cancer properties of Quercetin in breast cancer. Life Sciences. 2020 May 1;248:117463; Murakami A, Ashida H, Terao J. Multitargeted cancer prevention by quercetin. Cancer letters. 2008 Oct 8;269(2):315-25.].
Other than cancer, polyphenols are also proven to possess medicinal applications in various diseases such as inflammation, bacterial infections, gouty arthritis as xanthine oxidase inhibitor, coronary heart disease, diabetes, eye disorders, osteoporosis, peptic ulcers, neurodegenerative diseases, prostatitis, viral infections, etc. [Lakhanpal P, Rai DK. Quercetin: a versatile flavonoid. Internet Journal of Medical Update. 2007 Jul 1;2(2):22-37.].
Thus, the versatile therapeutic utility of polyphenols as well as boron compounds is well-established from past research. However, conjugation with borons may enhance its anticancer potential as borons are well known to possess anticancer properties. Hence, the development of polyphenolic-boron adducts by the application of synthetic and medicinal chemistry may help to enhance its anticancer potential. The introduction of boron moiety on polyphenols has helped us to increase its therapeutic potential against cancer.
Therefore, it is an objective of the invention to synthesize novel polyphenolic-boron adducts as anticancer agents, possessing therapeutic activity in the micromolar ranges and uses thereof.
SUMMARY OF THE INVENTION
Compounds having formula S, their method of synthesis and uses thereof are described herein.

(S)
wherein;
Unsubstituted/substituted phenylboronic acid is linked to two hydroxy groups at 5 and 7 position of quercetin, with an ester linkage;
R1 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones;
R2 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones;
R3 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones;
R4 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones;
R5 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones;
R6 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones.
The method of synthesis of compounds of formula (S) comprises of the following reaction;
i. Synthesis of polyphenolic boron adducts by condensation of substituted phenyl boronic acid with quercetin, in presence of anhydrous sodium sulphate in diethyl ether; or freshly distilled methanol; or freshly distilled acetone (Scheme 1)
The process is shown in Scheme 1 below:

Scheme 1
In another aspect, the compound of formula (S) of the present invention comprises;
1. 4-(2-(3,4-Dihydroxyphenyl)-3-hydroxy-4-oxo-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-7-yl)benzaldehyde (Sa)
2. 7-(3,4-Dichlorophenyl)-2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-4-one (Sb)
3. 4-(2-(3,4-Dihydroxyphenyl)-3-hydroxy-4-oxo-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-7-yl)benzoic acid (Sc)
4. 2-(3,4-Dihydroxyphenyl)-7-(4-fluorophenyl)-3-hydroxy-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-4-one (Sd)
5. 4-(2-(3,4-Dihydroxyphenyl)-3-hydroxy-4-oxo-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-7-yl)benzonitrile (Se)
DESCRIPTION OF FIGURES
Fig 1 depicts in vitro anticancer activity of compounds with general formula (S) against various cancer cell lines
DETAILED DESCRIPTION OF THE INVENTION
Throughout the disclosure the following terms, unless otherwise indicated, shall be understood to have the following meanings:
In the present specification, the term cancer is pathological condition characterized by uncontrolled proliferation of cells,
Proliferation refers to the rapid increase in the number of cells,
Polyphenols refers to a class of compounds containing more than one hydroxyl groups in their chemical structure,
Quercetin refers to a yellow crystalline pigment present in plants, used as a food supplement to reduce allergic responses or boost immunity,
Reactive Oxygen Species is a type of unstable molecule that contains oxygen and that easily reacts with other molecules in a cell,
MTT assay refers to a colorimetric assay for measuring cell metabolic activity using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide.
The compounds of formula (S) may contain asymmetric carbon atom and some of the compounds of this invention may contain one or more asymmetric centres and may thus give rise to stereoisomers and diastereomers. Although the compound of formula (S) is not depicted with any stereo centres, the present invention includes such stereoisomers and diastereomers, as well as the racemic and resolved, enantiomerically pure R and S stereoisomers, as well as other mixture of the R and S stereoisomers. The compound of formula (S) may exhibit geometrical isomerism including cis-trans and Z-E forms. So, the present invention comprises the individual geometrical isomers and stereoisomers.
Such isomers or diastereomers can be separated from their mixtures, by the application or adaptation of known methods, for example chromatographic techniques and recrystallization techniques, or they are separately prepared from the appropriate isomers of their intermediates. All forms are within the scope of the invention.
The present invention relates to synthesis of novel polyphenolic boron adducts of formula (S) or its pharmaceutically acceptable salts, solvates, isomers, enantiomers, any sort of formulation, and uses thereof;

(S)
wherein;
Unsubstituted/substituted phenylboronic acid is linked to two hydroxy groups at 5 and 7 position of quercetin, with an ester linkage;
R1 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones;
R2 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones;
R3 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones;
R4 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones;
R5 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones;
R6 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones.
The compounds of general formula (S) of the present invention comprise;
Table 1: Chemical structure and IUPAC name of compound with general formula (S)
Comp. No. Chemical Structure IUPAC name
Sa
4-(2-(3,4-Dihydroxyphenyl)-3-hydroxy-4-oxo-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-7-yl)benzaldehyde
Sb
7-(3,4-Dichlorophenyl)-2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-4-one
Sc
4-(2-(3,4-Dihydroxyphenyl)-3-hydroxy-4-oxo-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-7-yl)benzoic acid
Sd
2-(3,4-Dihydroxyphenyl)-7-(4-fluorophenyl)-3-hydroxy-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-4-one
Se
4-(2-(3,4-Dihydroxyphenyl)-3-hydroxy-4-oxo-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-7-yl)benzonitrile

In another embodiment, the present invention discloses a process of making of novel polyphenolic boron adducts of formula (S), which comprises of the following reaction;
i. Synthesis of polyphenolic boron adducts by condensation of substituted phenyl boronic acid with quercetin, in presence of anhydrous sodium sulphate in diethyl ether (Scheme 1)
In step (i), an accurate quantity of substituted phenyl boronic acid (I) (0.01 mol) was weighed and placed in a 100 mL round bottom flask, 15 mL of solvent such as diethyl ether, methanol or acetone was added to the above flask and stirred continuously to form a clear solution. To the above reaction mixture finely powdered activated sodium sulphate (Na2SO4; 0.1 mol) was added with continuous stirring. quercetin (II) (0.01 mol) was added to the above reaction mixture in a single portion. The reaction was continued overnight at room temperature with continuous stirring. TLC was used to monitor the reaction. After completion of the reaction, the reaction mixture was filtered and the solvent in the filtrate was evaporated under vacuum. The residue thus obtained was recrystallized using ethanol to yield yellow crystals of the polyphenolic boron adduct with general formula (S).
The pharmaceutical composition of compounds of general formula (S) or its pharmaceutically acceptable salts, their isomers, enantiomers, solvates along with pharmaceutically employed excipients are administered in an effective therapeutic amount to a subject in need either orally or parenterally.
The active compound of general formula (S) will be present in such pharmaceutical compositions in amounts sufficient to provide the desired dosage amount. The compounds of general formula (S), for oral administration, can be combined with a suitable solid or liquid carrier or diluent and other pharmaceutically acceptable excipients to form capsules, tablets, powders, syrups, solutions, suspensions and the like. For parenteral administration, the compounds can be combined with sterile aqueous or organic media to form injectable solutions.
In another embodiment, the present invention provides pharmaceutical composition comprising the compounds of general formula (S) or its pharmaceutically acceptable salts, their isomers, enantiomers, solvates along with pharmaceutically employed excipients which may be useful in the treatment of PCOS, ovarian cancer, breast cancer, or other forms of cancer. The composition can be formulated as tablets, capsules, powders, syrups, solutions, suspensions and such like or as parenteral injectable.
In another embodiment, the in vitro anticancer activity of compounds with general formula (S) was studied various cell lines including breast cancer (MDA-MB-231, MCF-7), prostate cancer (PC-3) and cervical cancer (HeLa) cell lines.

The following example, which includes preferred embodiments, will serve to illustrate the practice of this invention, it being understood that the particulars shown are by way of example and for purpose of illustrative discussion of preferred embodiments of the invention.

Example 1: 4-(2-(3,4-Dihydroxyphenyl)-3-hydroxy-4-oxo-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-7-yl)benzaldehyde (Sa)
Anhydrous sodium sulphate (0.1 mol) was stirred in freshly distilled acetone (30 mL) in a 100 mL round bottom flask for 10 minutes. An accurately weighed quantity of quercetin (3.4 g; 0.01 mol) (II) was added to the above reaction mixture and stirred continuously to form a clear solution. Lastly, required quantity of 4-Formylphenyl boronic acid (1.5 g; 0.01 mol) was added and stirred overnight in anhydrous conditions. The reaction was monitored using thin layer chromatography. After completion of the reaction, mixture was filtered and filtrate was subjected to solvent evaporation under vacuum, that yielded a yellow coloured precipitated product (Sa).
Analysis:
Mass (m/z): 416.25
1H-NMR (DMSO-D6): ? 12.45 (s, 1H, hydroxyl), 10.74 (s, 1H, hydroxyl), 9.99 (s, 1H, Formyl), 9.55 (s, 1H, Hydroxyl), 7.95-7.93 (d, 2H, Ar-H), 7.83-7.82 (d, 2H, Ar-H), 7.64 (s, 1H, Ar-H), 7.54-7.49 (d, 1H, Ar-H), 6.85-6.84 (d, 1H, Ar-H), 6.37 (s, 1H, Ar-H), 6.15 ppm (s, 1H, Ar-H).
13C-NMR (DMSO-D6): ? 194.02 (-CHO), 176.37 (Aromatic C=O), 164.41, 161.26, 156.67, 148.23, 147.34, 145.59, 137.68, 136.26, 135.08, 128.83, 122.49, 120.51, 116.14, 115.60, 103.55, 98.71, 93.88 ppm.

Example 2: 7-(3,4-Dichlorophenyl)-2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-4-one (Sb)
Anhydrous sodium sulphate (0.1 mol) was stirred in freshly distilled methanol (30 mL) in a 100 mL round bottom flask for 10 minutes. An accurately weighed quantity of quercetin (3.4 g; 0.01 mol) (II) was added to the above reaction mixture and stirred continuously to form a clear solution. Lastly, required quantity of 3,4-Dichlorophenyl boronic acid (1.9 g; 0.01 mol) was added and stirred overnight in anhydrous conditions. The reaction was monitored using thin layer chromatography. After completion of the reaction, mixture was filtered and filtrate was subjected to solvent evaporation under vacuum, that yielded a yellow coloured precipitated product (Sb).
Analysis:
Mass (m/z): 456.10
1H-NMR (DMSO-D6): ? 12.45 (s, 1H, hydroxyl), 10.76 (s, 1H, hydroxyl), 9.56 (s, 1H, Hydroxyl), 7.91 (s, 1H, Ar-H), 7.67-7.69 (d, 1H, Ar-H), 7.64 (s, 1H, Ar-H), 7.57-7.56 (d, 1H, Ar-H), 7.51-7.49 (d, 1H, Ar-H), 6.85-6.84 (d, 1H, Ar-H), 6.37 (s, 1H, Ar-H), 6.15 (s, 1H, Ar-H).
13C-NMR (DMSO-D6): ? 176.38 (Aromatic C=O), 164.42, 161.26, 156.68, 148.23, 147.34, 145.59, 136.35 (2C, Ar-C-Cl), 136.27, 134.69, 133.38, 130.47, 122.50, 120.51, 103.55, 98.71, 93.88.
Example 3: 4-(2-(3,4-Dihydroxyphenyl)-3-hydroxy-4-oxo-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-7-yl)benzoic acid (Sc)
Anhydrous sodium sulphate (0.1 mol) was stirred in freshly distilled acetone (30 mL) in a 100 mL round bottom flask for 10 minutes. An accurately weighed quantity of quercetin (3.4 g; 0.01 mol) (II) was added to the above reaction mixture and stirred continuously to form a clear solution. Lastly, required quantity of 4-Carboxyphenyl boronic acid (1.66 g; 0.01 mol) was added and stirred overnight in anhydrous conditions. The reaction was monitored using thin layer chromatography. After completion of the reaction, mixture was zfiltered and filtrate was subjected to solvent evaporation under vacuum, that yielded a yellow coloured precipitated product (Sc).
1H-NMR (DMSO-D6): ? 12.45 (s, 1H, hydroxyl), 12.43 (s, 1H, -COOH), 10.74 (s, 1H, hydroxyl), 9.54 (s, 1H, Hydroxyl), 7.81-7.80 (d, 2H, Ar-H), 7.79-7.78 (d, 2H, Ar-H), 7.64 (s, 1H, Ar-H), 7.51-7.49 (d, 1H, Ar-H), 6.85-6.84 (d, 1H, Ar-H), 6.37 (s, 1H, Ar-H), 6.15 (s, 1H, Ar-H).
13C-NMR (DMSO-D6): ? 176.38 (Aromatic C=O), 165.12 (-COOH), 164.42, 163.49, 161.26, 156.68, 148.24, 147.35, 145.59, 137.07, 137.01, 136.26, 122.50, 120.51, 116.14, 115.61, 114.87, 114.74, 103.55, 98.71, 93.88.
Example 4: 2-(3,4-Dihydroxyphenyl)-7-(4-fluorophenyl)-3-hydroxy-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-4-one (Sd)
Anhydrous sodium sulphate (0.1 mol) was stirred in freshly distilled acetone (30 mL) in a 100 mL round bottom flask for 10 minutes. An accurately weighed quantity of quercetin (3.4 g; 0.01 mol) (II) was added to the above reaction mixture and stirred continuously to form a clear solution. Lastly, required quantity of 4-Fluorophenyl boronic acid (1.4 g; 0.01 mol) was added and stirred overnight in anhydrous conditions. The reaction was monitored using thin layer chromatography. After completion of the reaction, mixture was filtered and filtrate was subjected to solvent evaporation under vacuum, that yielded a yellow coloured precipitated product (Sd).
Analysis:
Mass (m/z): 406.15
1H-NMR (DMSO-D6): ? 12.45 (s, 1H, hydroxyl), 10.73 (s, 1H, hydroxyl), 9.54 (s, 1H, Hydroxyl), 7.87-7.85 (d, 2H, Ar-H), 7.83-7.84 (d, 2H, Ar-H), 7.64 (s, 1H, Ar-H), 7.51-7.49 (d, 1H, Ar-H), 6.85-6.84 (d, 1H, Ar-H), 6.37 (s, 1H, Ar-H), 6.15 (s, 1H, Ar-H).
13C-NMR (DMSO-D6): ? 176.38 (Aromatic C=O), 168.03 (Ar-C-F), 164.41, 161.26, 156.67, 148.23, 147.34, 145.59, 136.26, 134.64, 132.48, 128.63, 122.49, 120.51, 116.14, 115.60, 103.55, 98.71, 93.88.
Example 5: 4-(2-(3,4-Dihydroxyphenyl)-3-hydroxy-4-oxo-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-7-yl)benzonitrile (Se)
Anhydrous sodium sulphate (0.1 mol) was stirred in freshly distilled acetone (30 mL) in a 100 mL round bottom flask for 10 minutes. An accurately weighed quantity of quercetin (3.4 g; 0.01 mol) (II) was added to the above reaction mixture and stirred continuously to form a clear solution. Lastly, required quantity of 4-Cyanophenyl boronic acid (1.47 g; 0.01 mol) was added and stirred overnight in anhydrous conditions. The reaction was monitored using thin layer chromatography. After completion of the reaction, mixture was filtered and filtrate was subjected to solvent evaporation under vacuum, that yielded a yellow coloured precipitated product (Se).
Analysis:
Mass (m/z): 413.10
1H-NMR (DMSO-D6): ? 12.45 (s, 1H, hydroxyl), 10.74 (s, 1H, hydroxyl), 9.55 (s, 1H, Hydroxyl), 7.90-7.89 (d, 2H, Ar-H), 7.75-7.74 (d, 2H, Ar-H), 7.64 (s, 1H, Ar-H), 7.51-7.49 (d, 1H, Ar-H), 6.86-6.84 (d, 1H, Ar-H), 6.37 (s, 1H, Ar-H), 6.15 (s, 1H, Ar-H).
13C-NMR (DMSO-D6): ? 176.38 (Aromatic C=O), 164.41, 161.26, 156.68, 148.23, 147.34, 145.59, 136.26, 135.15, 134.64, 131.28, 131.53, 122.50, 120.52, 119.54 (-CN), 116.14, 115.60, 112.97 (Ar-C-CN), 103.55, 98.71, 93.88.

BIOLOGICAL EVALUATION
Procedure for evaluation of in vitro anticancer potential:
The anticancer potential of compounds with general formula S (Sa-Se) was determined using MTT [(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide)] assay against cancer cell lines of different origin including breast (MDA-MB-231, MCF-7), Prostate (PC-3) and Cervical cancer (HeLa). Quercetin was used as a positive control for the in vitro assay. Assays were carried out at the time intervals of 24 hours, 48 hours and 72 hours, and IC50 values were calculated at the respective time intervals.

Results of in vitro anticancer assay:
Polyphenolic-boron adducts with general formula S (Sa-e) were evaluated in vitro against cancer cell lines of different origin for their anticancer activity using procedure described elsewhere [Nayak J, Prajapati KS, Kumar S, Sahoo SK, Kumar R. Synthesis of thiolated chlorogenic acid-capped silver nanoparticles for the effective dual action towards antimicrobial and anticancer therapy. Colloid and Polymer Science. 2022 Sep;300(9):1037-47.]. Quercetin was used as reference standard. In general, the synthesized molecules showed potential cell proliferation inhibition in test cell lines of different origins, including breast (MCF-7, MDA-MB-231), prostate (PC-3) and ovarian cancer (HeLa) at 24, 48 and 72 hours time intervals. Compound (Sb) showed greater antiproliferative activity in test cell lines of different origins at respective time intervals as compared to quercetin (Table 1(a) and 1(b) and Figure 1). In MDA-MB-231 cell lines, Sb was observed to possess 4.67% and 14.24% better IC50 values as compared to quercetin at 48 and 72 hours, respectively, whereas in MCF-7 cell lines, IC50 values of Sb was observed to be 11.80%, 35.73% and 35.55% better as compared to quercetin at 24, 48 and 72 hours, respectively. Also, in PC-3 cancer cell lines, Sb was observed to possess 7.79% and 27.45% better IC50 values as compared to quercetin at 48 and 72 hours, respectively, whereas in HeLa cell lines, IC50 values of Sb was observed to be 18.05%, 41.63% and 41.35% better as compared to quercetin at 24, 48 and 72 hours, respectively.
Table 1(a): In vitro anticancer activity of compounds with general formula (S) against breast cancer cell lines
C no. IC50 (?M) of the compounds with general formula (S) at 24, 48, 72 h
MDA-MB-231 MCF-7
24h 48h 72h 24h 48h 72h
(Sa) - - - - - 76.79±0.12
(Sb) - 64.24±1.42 45.059±1.71 64.564±2.11 27.583±0.78 20.641±0.85
(Sc) - - - - 97.480±1.39 57.562±1.79
(Sd) - - 98.37±1.30 - 57.41±0.34 53.71±1.55
(Se) - 97.06±1.76 80.656±2.67 81.337±1.65 59.891±9.06 44.239±5.12
Quercetin - 67.39±0.65 52.504±0.90 73.208±0.79 42.919±0.33 32.027±1.54

Table 1(b): In vitro anticancer activity of compounds with general formula (S) against prostate cancer and ovarian cancer cell lines
C no. IC50 (?M) of the compounds with general formula (S) at 24, 48, 72 h
PC-3 HeLa
24h 48h 72h 24h 48h 72h
(Sa) - - 98.93±1.5 - - 49.01±4.42
(Sb) - 68.10±3.04 36.81±4.11 67.76±2.83 31.875±1.18 25.713±0.33
(Sc) - - - - 94.893±0.79 76.478±2.5
(Sd) - - 73.9±5.61 - - 52.09±0.42
(Se) - - 62.75±3.31 55.15±3.54 43.956±0.41 40.875±0.25
Quercetin - 73.86±1.23 50.74±1.34 82.69±2.03 54.608±0.91 43.845±0.27

We claim;

1. Polyphenolic boron adducts with general formula (S) as anticancer agents or its pharmaceutically acceptable salts, solvates, isomers, enantiomers, any sort of formulation, and uses thereof;

(S)
wherein;
Unsubstituted/substituted phenylboronic acid is linked to two hydroxy groups at 5 and 7 position of quercetin, with an ester linkage;
R1 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones;
R2 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones;
R3 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones;
R4 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones;
R5 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones;
R6 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones.
2. The compounds of general formula (S) according to claim 1 comprises;
i. 4-(2-(3,4-Dihydroxyphenyl)-3-hydroxy-4-oxo-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-7-yl)benzaldehyde (Sa)
ii. 7-(3,4-Dichlorophenyl)-2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-4-one (Sb)
iii. 4-(2-(3,4-Dihydroxyphenyl)-3-hydroxy-4-oxo-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-7-yl)benzoic acid (Sc)
iv. 2-(3,4-Dihydroxyphenyl)-7-(4-fluorophenyl)-3-hydroxy-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-4-one (Sd)
v. 4-(2-(3,4-Dihydroxyphenyl)-3-hydroxy-4-oxo-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-7-yl)benzonitrile (Se)

3. The process for preparation of unsubstituted/substituted polyphenolic boron adducts of general formula (S) or its pharmaceutically acceptable salts, solvates, isomers, enantiomers thereof according to claim 1

(S)
wherein;
Unsubstituted/substituted phenylboronic acid is linked to two hydroxy groups at 5 and 7 position of quercetin, with an ester linkage;
R1 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones;
R2 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones;
R3 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones;
R4 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones;
R5 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones;
R6 is independently selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH) or their salts; substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones.
The compounds of general formula (S) according to claim 1 comprises;
i. 4-(2-(3,4-Dihydroxyphenyl)-3-hydroxy-4-oxo-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-7-yl)benzaldehyde (Sa)
ii. 7-(3,4-Dichlorophenyl)-2-(3,4-dihydroxyphenyl)-3-hydroxy-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-4-one (Sb)
iii. 4-(2-(3,4-Dihydroxyphenyl)-3-hydroxy-4-oxo-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-7-yl)benzoic acid (Sc)
iv. 2-(3,4-Dihydroxyphenyl)-7-(4-fluorophenyl)-3-hydroxy-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-4-one (Sd)
v. 4-(2-(3,4-Dihydroxyphenyl)-3-hydroxy-4-oxo-4H-5,9-(metheno)pyrano[3,2-e][1,3,2]dioxaborocin-7-yl)benzonitrile (Se)
Comprising the following reaction (step i);
i. Synthesis of polyphenolic boron adducts by condensation of substituted phenyl boronic acid with quercetin, in presence of anhydrous sodium sulphate in diethyl ether; or freshly distilled methanol; or freshly distilled acetone (Scheme 1)
4. The process according to claim 3, wherein the substitution at R1 of compound having general formula (S) in step (i) is selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH); substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones.
5. The process according to claim 3, wherein the substitution at R2 is selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g.,-CH3); (un)-substituted or substituted linear or branched aryl; (un)-substituted or substituted heteroaryl; (un)-substituted or substituted alkylaryl; (un)-substituted or substituted alkylheteroaryl; (un)-substituted or substituted –CN; (un)-substituted or substituted -SO3H; (un)-substituted or substituted amines; (un)-substituted or substituted nitro or nitrites or nitrates; (un)-substituted or substituted esters or acids and the like.
6. The process according to claim 3, wherein the substitution at R3 of compound having general formula (S) in step (i) is selected from hydrogen; (un)-substituted or substituted linear or branched alkyl (e.g., -CH3, -C2H5, C3H7, C4H9, -CH2-CH2-Br, -CH2-CH2-CH2-Cl, -CH2-CH2-CH2-Br); (un)-substituted or substituted aryl or (un)-substituted or substituted alkylaryl (e.g., -CH2-C6H5, -CH2-p-Cl-C6H4); substituted or (un)-substituted, linear, branched hetero or cyclic alkyl, alkenyl, or alkynyl; substituted or (un)-substituted aryl or heteroaryl, halogen, substituted or (un)-substituted alkoxy; substituted or (un)-substituted hydroxyl; substituted or (un)-substituted cyano; substituted or (un)-substituted formyl; substituted or (un)-substituted acyl; substituted or (un)-substituted carboxylic acid (e.g., -CH2-COOH); substituted or (un)-substituted carboxylate; substituted or (un)-substituted primary or secondary or tertiary amide; substituted or (un)-substituted secondary or tertiary carbamate; substituted or (un)-substituted urea; substituted or (un)-substituted carbine; substituted or (un)-substituted ester (e.g., -COOC2H5, -CH2-COOC2H5); substituted or (un)-substituted thiol; substituted or (un)-substituted primary or secondary or tertiary amine; substituted or (un)-substituted thioether; substituted or (un)-substituted sulfinyl group; and substituted or (un)-substituted sulfonyl group; substituted or (un)-substituted ketones.
7. The process according to claim 3, wherein the solvent in step (i) is selected from polar aprotic such as acetonitrile THF, acetone, DMF, DMSO and the like; or polar protic such as ethanol, methanol, n-propyl alcohol, isopropyl alcohol and the like.
8. The pharmaceutical composition comprising the compounds of general formula (S) or is pharmaceutically acceptable salts, their isomers, enantiomers, solvates according to claim 1 along with pharmaceutically employed excipients associated with cancer-related complications, including insulin resistance, hyperandrogenism for the management of cancer and its complications, or any sort of biological activity either alone or in combination with other compounds.