Description: Background of the invention: Edaravone is a FDA approved drug since May 2017. It is the first free radical scavenger among pyrazolinones that can be used as a neuroprotective agent (Eur. J. Med. Chem. 2020, 210, 113061). Pyrazolinone derivative was used against myocardial ischemia and some derivatives of it were also used for the treatment of Human Immunodeficiency Syndrome (HIV) and Acquired Immunodeficiency Syndrome (AIDS) (Eur. J. Med. Chem. 2009, 44, 3852-3857). Furthermore, it treats nearly fifty percent of ischemic stroke patients in Japan. It also treats spinal cord and lung injuries (Stroke. 2019, 50, 1805-1811). It regulates the prominent antioxidative protein hemeoxygenase and has been proven beneficial in ischemic injuries like hypoxia-inducible factor (HIF) (Oxid. Med. Cell. Longev. 2018, 2018 5216383). Moreover, it has been used as a protective agent for cardiovascular diseases resulting from oxidative stress (EP3431075A1, 2017) cytokine-induced apoptosis, and diabetic cardiomyopathy. Due to its free radical scavenging properties, it acts as a novel brain protectant used clinically for reducing ischemic cerebral infarction (Mol. Pharm. 2020, 17, 3192-3201). The above mentioned characteristics in clinics make it suitable for different populations (J. Chem. Eng. Data. 2020, 65, 3240-3251). The biochemical measures were executed to assess the intuitive impact of the persistent effect of edaravone on oxidative stress biomarkers (Psychiatry Res. 2019, 281, 112577). In amyotrophic lateral sclerosis (ALS) patients, intravenous edaravone showed no severe side effects (Neurol. Sci. 2019, 40, 235-241; USO10987341B2, 2021). In animal models of Parkinson’s disease, it also showed some beneficial neuroprotective effects (J. Enzyme Inhib. Med. Chem. 2020, 35, 1596-1605). In combination with caffeine, it acted as an inhibitor of the adenosine A2A receptor. This combination effectively removes cognitive impairment and muscle weakness associated with Parkinson’s disease due to edaravone’s capability of scavenging peroxynitrite free radicals (EP3666270A1, 2020; Neurosci. Lett. 2019, 711, 134438; Toxicol. Appl. Pharmacol. 2019, 380, 114689). Furthermore, edaravone, combined with thrombolytic drugs, protects the integrity of blood vessels and neurons (Curr. Drug Targets. 2020, 21, 776-780). It has also been reported that edaravone exhibits neuroprotective effects by inhibiting inflammation and vascular endothelial injury (J. Cereb. Blood Flow Metab. 2021, 41,1437–1448).
Summary of the invention:
The present invention discloses the anticancer screening of some new edaravone derivatives against lung cancer cell line (A549). The compounds 6a, 6b, 6c & 6g were found to display excellent potential than standard drug carboplatin against the lung cancer cell line (A549)
Detailed description of the invention:
Anticancer Activity Evaluation
To demonstrate the versatility of the synthesized compounds (Fig.1), we evaluated their anti-cancer potential against lung cancer cell line.

Fig. 1. Various substitution patterns on the pyrazole moiety
To explore the anticancer potential, all synthesized derivatives of edaravone were screened for their antiproliferative activity against human lung adenocarcinoma epithelial cell line A549. The starting experimental concentrations of all the test compounds, standard anticancer drug carboplatin, and cisplatin were of 500 µM as display in bar graph in Fig. 2. All compounds displayed anticancer activity towards human lung adenocarcinoma cell line A549. Compounds 6a, 6b, 6c & 6g have been found to exhibit excellent activity with IC50 values 91.87 ± 13.3, 120.37 ± 9.8, 132.87 ± 11.4 & 170.03 ± 7.6, respectively as compared to standard drug, carboplatin (IC50 = 187.5 ± 6.5) while 6j was least effective with IC50 value 668 ± 16.1 (Table-1). Furthermore, the compounds 6f, 6h, 6d, 6i & 6e exhibited moderate antiproliferative activity than carboplatin with more IC50 values. The SAR study revealed that substitution on 4th position of the aromatic ring linked to pyrazole moiety decreases the anticancer potential of the compound. In case of aryl substitution at position-3 of pyrazole nucleus, anticancer potential decreases in order of Br ? OH ? Cl ? Me ? OMe ? F.
Table 1. Influence of the compounds 6a-j on the lung cancer cell line A549 (In vitro anticancer IC50 (µM)
Compound IC50 (µM) ± SEM.
6a 91.87 ± 13.3
6b 120.37 ± 9.8
6c 170.03 ± 7.6
6d 224.57 ± 3.8
6e 390.6 ± 3.7
6f 193.2. ± 7.6
6g 132.87 ± 11.4
6h 198.23 ± 6.7
6i 312.83 ± 11.7
6j 668.2 ± 16.1
Cisplatin 43.38 ± 8.5
Carboplatin 187.5 ± 6.5

(A) (B)
Fig. 2. Percentage of A549 viable cells on treatment with varying concentrations of compounds. (A) on treatment with compounds 6d, 6g, 6h, 6i & 6j; (B) on treatment with compounds, 6a, 6b 6c, 6e & 6f
Outcome of the Invention:
Compounds 6a, 6b, 6c & 6g showed growth inhibitory effects on lung cancer cell line, with IC50 values 91.87 ± 13.3, 120.37 ± 9.8, 132.87 ± 11.4 & 170.03 ± 7.6, respectively. Therefore, compound 6a, 6b, 6c & 6g have emerged as potential therapeutics for lung cancer in future.
Highlights of the Invention:
? Explored new edaravone derivatives 6a, 6b, 6c & 6g as new anticancer agents for lung cancer.
Experimental:
Anticancer activity
Cell Culture
A549 cells (Human lung adenocarcinoma cells) were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS: Gibco) and Penicillin-Streptomycin with a continuous supply of 5 % CO2 at 37? in CO2 incubator.
Cell viability assay
Cell viability was investigated with an MTT assay using yellow (3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) salt. After the Culture reached sufficient confluency, cells were harvested with 0.25% trypsin-EDTA. Cell counting was done with a hemocytometer. In 96 well plates, 1x 104cells/well and incubated for 24 hr in a CO2 incubator for cell attachment and growth. After 24 hr, test compounds with varying concentrations (starting from 500µM as highest concentration) were added to the culture plate and incubated for 48 hr. The viability of the treated cell culture with test compounds was assessed after 48 hr of incubation. The wells were gently washed with 1X phosphate buffer saline (PBS) to remove the test compounds and MTT salt solution (5mg/mL in 1X PBS) and incubated at 37 ?. After 3 hr of incubation, DMSO was used to solubilize the formazan crystal and incubated for 30 minutes. The 96 well plates were then read for absorbance in a SynergyH1 microplate reader at 570 nm. IC50 values were calculated for each test compound in GraphPad Prism 8.0.1 by fitting the experimental results to the sigmoidal equation , Claims:I/We claim
1. The compounds of the formula I, where Ar is C6H5, BrC6H4, OHC6H4, ClC6H4 as anticancer agents for lung cancer cell line (A549) at different concentrations.

2. Compounds as claimed in claim 1, wherein the said compound reduces cell viability of lung cancer cells (A549) up to 38.78% in 48 hours cell viability assay.
3. A compound as claimed in claim 1, wherein the said compound can be used in concentrations upto 500 µM.
4. A compound as claimed in claim 1, wherein the said compounds reduce cell viability of lung cancer cells (A549) upto 59-70 % at 10 µM after 48 hours treatment whereas standard drug Carboplatin reduces upto 77.91% cell viability.
5. A compound as claimed in claim 1, wherein the said compounds reduce cell viability of lung cancer cells (A549) upto 48-54 % at 125 µM after 48 hours treatment whereas standard drug Carboplatin reduces upto 60.45% cell viability.