DESC:A Multicomponent Process for Peptoid Synthesis with Anti-Quorum Sensing Properties

Field of Invention:
The present invention describes the synthesis and characterization of novel peptoids under simple reaction conditions with no catalyst via multicomponent approach. The synthesized compounds (peptoids) exhibit very good biological activity as anti-quorum sensing agents which in future would be used as potential candidates in combating bacterial infections and antibiotic resistance.

Background of Invention:
In the environment, several microbial taxa control the regulation of virulence and biofilm by a cell-to-cell communication system referred to as quorum sensing (QS). Targeting the quorum sensing (QS) system of such microbial communities has become a promising strategy for combating microbial infections. Inhibiting QS can also disrupt the formation of biofilms, which serve as a protective mechanism for microbes against host defenses and antimicrobial agents [1-2]. For this, development of architectures, namely peptoids could serve as potential candidates which could target the QS system. Peptoids are peptidomimetics that prevent proteolytic degradation by repositioning the side-chain from the a-carbon (as they are in amino acids) to the amide nitrogen [3]. Zuckermann et al. developed a general methodology wherein peptoids are routinely synthesized on Rink amide linker-derivatized solid supports using the submonomer synthesis method [4]. Due to their improved proteolytic stabilities [5] and greater cellular permeabilities [6,7] compared to peptides, peptoids have been investigated as tools for studying biomolecular interactions [8,9] and have shown significant potential for biological and therapeutic applications [10].
The development of an efficient synthetic route toward polypeptoids under benign conditions is highly desirable and yet a challenge. For this, multiple component reactions (MCRs) are very well known for generating a diverse array of compounds as they proceed through a sequential synthesis in one-pot with three or more starting compounds. Ugi reaction has been a boon in polypeptoids chemistry as it offers effective construction of peptoid backbones [11]. Ugi reaction (Scheme 1) is one of the most efficient multicomponent reactions involving four components in a one pot, in which an acid, an isocyanide, an aldehyde or ketone and an amine react to form a bis-amide. The reaction utilizes simple reaction conditions, no catalyst is used, there is 100% atom economy and generally products are formed in good yields.

Scheme 1. General one-pot Ugi reaction
The Ugi reaction products are peptidomimetics with potential therapeutic uses that can demonstrate a wide range of substitution patterns. Therefore, such compounds have potential applications as drug and gene vehicles, bioseparation films, antimicrobial agents, and other therapeutics [12-20]. In view of potential applications of peptoids, we designed and synthesized compounds via Ugi reaction for their potential applications in combating bacterial infections. As antibiotic resistance continues to pose a significant threat, this approach represents a promising alternative approach for controlling microbial infections.
Detailed description of the invention:
As mentioned above, multicomponent reactions enable the quick insertion of structural alterations that result in the desired properties, making them effective tools for the synthesis of diverse array of compounds [21]. In a highly convergent process, the Ugi four-component condensation [22] is a prototypical method for synthesizing peptoids, and it has also been utilised to create tripeptoid compounds [23]. According to the previously reported method, we utilized Ugi four component reaction to achieve the target compounds with slight modifications [24-28]. In this study, nine new peptoids have been synthesized via a multicomponent isocyanide based Ugi reaction by specifically incorporating long alkyl chain of 18 carbons at the carbonyl center. Further, it discloses that such compounds could be potential candidates for QS systems in microbes.

All the starting materials, reagents and solvents were obtained from commercial suppliers (Sigma-Aldrich, Central Drug House etc.) and used directly without any purifications. The reactions, unless otherwise noted were carried out in oven dried glassware under nitrogen atmosphere.
Synthesis of Ugi peptoids (5a-i) is outlined in Scheme 2. Initially, tryptamine (1) was added to a solution of variety of aldehydes in methanol (5 mL), the solution was stirred at room temperature for 1h. Then stearic acid was added which was then followed by cyclohexyl isocyanide addition. The reaction was monitored by TLC. The obtained crude product was purified the solvent mixture of EtOAc and hexane in 3:7, respectively. The desired products were isolated as solid in 60-70% yield. The products were characterized by recording their melting points and by analyzing their spectral data (IR, 1H, 13C NMR, and HRMS).

Scheme 2. Synthesis of novel peptoids via Ugi one-pot four component reaction

Figure 1. Structures of synthesized novel peptoids

A broad singlet near d 8.17 in 1H NMR spectra confirms -NH of the indole nucleus (5a). In 13C NMR spectrum, d 174.5 and 169.1 ppm display the characteristic signals for assigning the location of carbonyl groups. In the FTIR spectrum, there are characteristic peaks at 3250 and 3082 cm-1, which are attributed to the NH bond stretching indole and amide. The peaks at 2914 and 2854 cm-1 correspond to the CH stretching of the alkyl chains, whereas the peak at 1646 cm-1 corresponds to the stretching vibration of the amide carbonyl >C=O functionality.

After successful characterization of the synthesized compounds, they were tested for their anti-QS activity using Agrobacterium tumefaciens NT1 as a reporter strain. A. tumefaciens, horizontal transfer and vegetative replication of oncogenic Ti plasmids involve a cell-to-cell communication process called quorum-sensing (QS). The determinants of the QS-system belong to the LuxR/LuxI class. The LuxI-like protein TraI synthesizes N-acyl-homoserine lactone molecules which act as diffusible QS-signals. Beyond a threshold concentration, these molecules bind and activate the LuxR-like transcriptional regulator TraR, thereby initiating the QS-regulatory pathway. AHLs with long N-acyl side chains can be detected by A. tumefaciens NT1 (traR, tra::lacZ749) at the lowest concentrations. Anti-QS compounds have promising prospects in the fight against bacterial infections and antibiotic resistance. Further research is needed to develop more effective and specific compounds and to evaluate their safety and efficacy.

Experimental Section

General method for synthesis of Ugi Peptoids (5a-i)

Tryptamine 1 (1 mmol), aldehyde 2 (1 mmol) were dissolved in methanol (5 mL) and stirred for 1 hour at room temperature. Then to the reaction mixture was added stearic acid 4 (1 mmol) which was then followed by the addition of cyclohexyl isocyanide 3 (1 mmol). The reaction mixture was stirred overnight at room temperature. Progress of reaction was monitored with the help of TLC. After completion of the reaction, solvents were dried under reduced pressure. Then CH2Cl2 was added and the organic layer was washed twice with saturated Na2CO3 solution. After drying the organic layer over Na2SO4, the solvent was removed in vacuo and the crude product was purified by column chromatography and/or recrystallisation (Scheme I).

Anti-quorum sensing activity assay: The Agrobacterium tumefaciens NT1 biosensor strain was incubated for 48 hours at 30° C in a static condition with gentamicin at a concentration of 50 mg/ml in Luria broth. We used 20 mg/ml of freshly prepared X-gal in DMSO. 300 µl of AHL, 300 µl of X-gal, and 50 µl of gentamicin were mixed before pouring it onto the media plate, spreading it evenly, and letting it dry. On the same plate, a bacterial lawn of the biosensor strain was prepared. Wells were prepared and the compounds were added into each well and plates were incubated for 48 hours. Briefly, zone of anti-QS activity (Z) = R-X, where R is the complete zone surrounding the well. X is the zone of anti-microbial activity (No bacterial growth), and Z is the final anti-quorum sensing zone was determined.

Results and Discussions

Characterization data of the compounds 5a-i.
N-(2-(1H-Indol-3-yl)ethyl)-N-(2-(cyclohexylamino)-2-oxo-1-phenylethyl)stearamide (5a):
Yield: 70%; off-white solid; m.p. = 118-120°C; IR (neat): ?max = 3265 (NH str.), 1646 (CO str.), cm-1. 1H NMR (400 MHz, CDCl3) d 8.17 (s, 1H), 7.39 (s, 2H), 7.31 (d, J = 7.7 Hz, 3H), 7.24 (dd, J = 8.0, 2.8 Hz, 2H), 7.07 (s, 1H), 6.99 (d, J = 7.7 Hz, 1H), 6.74 (d, J = 2.1 Hz, 1H), 5.85 (d, J = 4.7 Hz, 2H), 3.83-3.67 (m, 1H), 3.60-3.45 (m, 2H), 2.85-2.69 (m, 1H), 2.46-2.19 (m, 3H), 1.83 (dd, J = 8.1, 3.8 Hz, 2H), 1.77-1.63 (m, 1H), 1.65-1.45 (m, 5H), 1.18 (d, J = 4.3 Hz, 29H), 1.04 (d, J = 12.7 Hz, 3H), 0.81 (t, J = 6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) d 174.5 (s), 169.1 (s), 136.1 (s), 135.8 (s), 129.5 (s), 128.8 (s), 128.4 (s), 127.0 (s), 122.0 (d, J = 5.9 Hz), 119.3 (s), 118.3 (s), 112.4 (s), 111.2 (s), 62.7 (s), 48.5 (s), 47.7 (s), 33.6 (s), 32.8 (s), 31.9 (s), 30.9 (s), 29.9-29.2 (m), 25.8 (s), 25.5 (d, J = 4.7 Hz), 24.7 (d, J = 4.5 Hz), 22.7 (s), 14.1 (s); HRMS calcd. for C42H63N3O2 [M+Na+], 664.4812; found, 664.4808.
N-(2-(1H-Indol-3-yl)ethyl)-N-(1-(4-cyanophenyl)-2-(cyclohexylamino)-2-oxoethyl)-stearamide (5b):
Yield: 69%; white solid; m.p. = 115-117°C; IR (neat): ?max = 3265 (NH str.), 2221 (CN str.), 1641(CO str.) cm-1; 1H NMR (400 MHz, CDCl3) d 8.19 (s, 1H), 7.54 (s, 2H), 7.45 (s, 2H), 7.33 (s, 1H), 7.25 (s, 1H), 7.12 (s, 1H), 7.05 (s, 1H), 6.81 (s, 1H), 6.36 (d, J = 7.7 Hz, 1H), 5.74 (s, 1H), 3.85-3.67 (m, 1H), 3.64-3.51 (m, 2H), 3.41 (q, J = 7.0 Hz, 4H), 2.91 (s, 1H), 2.72-2.53 (m, 1H), 2.40-2.22 (m, 2H), 1.83 (s, 2H), 1.69 – 1.41 (m, 5H), 1.15 (dd, J = 16.4, 9.4 Hz, 29H), 0.80 (t, J = 6.7 Hz, 3H); 13C NMR (101 MHz, CDCl3) d 174.8 (s), 168.2 (s), 141.3 (s), 136.2 (s), 132.3 (s), 129.2 (s), 126.9 (s), 122.2 (d, J = 10.7 Hz), 119.6 (s), 118.2 (s), 111.8 (d, J = 7.9 Hz), 111.3 (s), 77.3 (s), 77.0 (s), 76.7 (s), 65.8 (s), 63.1 (s), 48.6 (d, J = 9.1 Hz), 33.5 (s), 32.7 (d, J = 9.3 Hz), 31.9 (s), 29.8-29.2 (m), 25.8 (s), 25.4 (s), 24.6 (s), 22.7 (s), 15.2 (s), 14.1 (s). HRMS calcd. for C43H62N4O2 [M+H+], 667.4946; found, 667.4945.

N-(2-(1H-Indol-3-yl)ethyl)-N-(2-(cyclohexylamino)-2-oxo-1-(p-tolyl)ethyl)stearamide (5c):
Yield: 67%; white solid; m.p. 99-101°C; IR (neat): ?max = 3292 (NH str.), 1645 (CO str.) cm-1; 1H NMR (400 MHz, CDCl3) d 8.15 (s, 1H), 7.29 (d, J = 8.0 Hz, 2H), 7.21 (dd, J = 16.9, 7.8 Hz, 3H), 7.13 (d, J = 8.0 Hz, 2H), 7.07 (s, 1H), 6.97 (s, 1H), 6.77 (d, J = 2.1 Hz, 1H), 5.81 (s, 2H), 3.84-3.66 (m, 1H), 3.49 (d, J = 8.2 Hz, 2H), 2.84-2.67 (m, 1H), 2.37-2.17 (m, 6H), 1.81 (d, J = 3.1 Hz, 2H), 1.56 (s, 5H), 1.19 (t, J = 7.8 Hz, 29H), 1.03 (dd, J = 12.1, 3.1 Hz, 3H), 0.80 (d, J = 7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3) d 174.4 (s), 169.3 (s), 138.3 (s), 136.1 (s), 132.7 (s), 129.5 (d, J = 2.8 Hz), 127.1 (s), 122.0 (d, J = 5.0 Hz), 119. (s), 118.4 (s), 112.5 (s), 111.2 (s), 77.3 (s), 77.0 (s), 76.7 (s), 62.5 (s), 48.5 (s), 47.5 (s), 33.6 (s), 32.8 (s), 31.9 (s), 29.8-29.2 (m), 25.7 (d, J = 28.0 Hz), 25.5 (s), 24.7 (s), 22.7 (s), 21.2 (s), 14.1 (s); HRMS calcd. for C43H65N3O2 [M+Na+], 678.4969; found, 678.4967.
N-(2-(1H-Indol-3-yl)ethyl)-N-(2-(cyclohexylamino)-1-(4-methoxyphenyl)-2-oxoethyl)-stearamide (5d):
Yield: 68%; white solid; m.p. 135-137°C; IR (neat): ?max = 3270 (NH str.), 1624 (CO str.), 1249 (CO str. O-CH3) cm-1; 1H NMR (400 MHz, CDCl3) d 8.21-8.12 (m, 1H), 7.41-7.27 (m, 2H), 7.27-7.17 (m, 2H), 7.09-7.04 (m, 1H), 7.01-6.95 (m, 1H), 6.90-6.82 (m, 2H), 6.78-6.75 (m, 1H), 5.93-5.65 (m, 2H), 3.74 (s, 3H), 3.62-3.39 (m, 2H), 2.76 (dt, J = 15.9, 8.0 Hz, 1H), 2.47-2.18 (m, 3H), 1.92-1.74 (m, 2H), 1.64-1.45 (m, 5H), 1.43-1.06 (m, 31H), 1.08-0.94 (m, 3H), 0.81 (t, J = 6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) d 174.4 (s), 169.3 (s), 159.6 (s), 136.1 (s), 130.9 (s), 127.7 (s), 127.1 (s), 122.0 (d, J = 3.7 Hz), 119.2 (s), 118.4 (s), 114.2 (s), 112.5 (s), 111.2 (s), 62.0 (s), 55.3 (s), 48.4 (s), 47.3 (s), 33.6 (s), 32.8 (d, J = 3.5 Hz), 31.9 (s), 29.9-29.2 (m), 25.8 (s), 25.5 (d, J = 3.6 Hz), 24.7(d, J = 5.0 Hz), 22.7 (s), 14.1 (s); HRMS calcd. for C43H65N3O3 [M+Na+], 694.4918; found, 694.4913.
N-(2-(1H-Indol-3-yl)ethyl)-N-(1-(4-chlorophenyl)-2-(cyclohexylamino)-2-oxoethyl)-stearamide (5e):
Yield: 65%; off-white solid; m.p. = 108-110°C; IR (neat): ?max = 3277 (NH str.), 1613 (CO str.) cm-1; 1H NMR (400 MHz, CDCl3) d 8.07 (s, 1H), 7.31 (d, J = 14.8 Hz, 6H), 7.05 (dt, J = 31.0, 7.2 Hz, 2H), 6.80-6.75 (m, 1H), 6.01 (d, J = 7.9 Hz, 1H), 5.77 (s, 1H), 3.82-3.67 (m, 1H), 3.52 (dd, J = 11.4, 7.7 Hz, 2H), 2.91-2.77 (m, 1H), 2.59-2.43 (m, 1H), 2.37-2.22 (m, 2H), 1.88-1.73 (m, 2H), 1.67-1.47 (m, 5H), 1.18 (d, J = 3.9 Hz, 30H), 1.09-0.96 (m, 3H), 0.80 (d, J = 7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3) d 174.6 (s), 168.7 (s), 136.1 (s), 134.36 (d, J = 3.5 Hz), 130.6 (s), 128.9(s), 127.0 (s), 122.1 (d, J = 8.8 Hz), 119.4 (s), 118.3 (s), 112.2 (s), 111.2 (s), 62.1 (s), 48.5 (s), 47. (s), 33.8 (s), 33.5 (s), 32. (d, J = 5.1 Hz), 31.9 (s), 29.8-29.0 (m), 25.8 (s), 25.5 (s), 24.7 (s), 22.7 (s), 14.1 (s). HRMS calcd. for C42H62ClN3O2 [M+K+], 714.4162; found, 714.4167.

N-(2-(1H-indol-3-yl)ethyl)-N-(2-(cyclohexylamino)-1-(4-(dimethylamino)phenyl)-2-oxoethyl)stearamide (5f):
Yield: 60%; off-white solid; m.p. = 110-112°C; IR (neat): ?max = 3393 (NH str.), 1625 (CO str.) cm-1; 1H NMR (400 MHz, CDCl3) d 8.05 (d, J = 23.9 Hz, 1H), 7.31-7.14 (m, 4H), 7.08 (dd, J = 16.8, 9.0 Hz, 1H), 6.95 (t, J = 7.5 Hz, 1H), 6.79 (d, J = 1.8 Hz, 1H), 6.65 (d, J = 8.7 Hz, 2H), 5.79 (s, 1H), 5.63 (d, J = 8.1 Hz, 1H), 3.73 (dt, J = 18.7, 7.3 Hz, 1H), 3.46 (dd, J = 22.1, 14.0 Hz, 2H), 2.90 (s, 5H), 2.79 – 2.67 (m, 1H), 2.48-2.17 (m, 3H), 1.98-1.71 (m, 3H), 1.70-1.37 (m, 6H), 1.19 (t, J = 9.3 Hz, 29H), 1.09-0.95 (m, 3H), 0.80 (d, J = 7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3) d 174.3 (s), 169.6 (s), 150. (s), 136.13 (s), 130.8 (s), 127.1 (s), 122.7 (s), 121.9 (d, J = 8.2 Hz), 119.1 (s), 118.6 (s), 112.8 (s), 112.4 (s), 111.1 (s), 62.0 (s), 48. (s), 47.1 (s), 40.4 (s), 33.6 (s), 32.9 (s), 31.9 (s), 29.8-29.2 (m), 25.8 (s), 25.5 (s), 24.8 (d, J = 6.8 Hz), 22.7 (s), 14.1 (s); HRMS calcd. for C44H68N4O2 [M+H+], 685.5415; found, 685.5414.
N-(2-(1H-Indol-3-yl)ethyl)-N-(2-(cyclohexylamino)-1-(2-nitrophenyl)-2-oxoethyl)stearamide (5g):
Yield: 61%; off-white solid; m.p. = 96-98°C, IR (neat): ?max = 3253 (NH str.), 1625 (CO str.), 1342 and 1531 (NO str.) cm-1; 1H NMR (400 MHz, CDCl3) d 8.19 (s, 1H), 8.08-7.98 (m, 1H), 7.87 (d, J = 7.9 Hz, 1H), 7.42 (m, J = 19.5, 13.4, 7.4 Hz, 4H), 7.29-7.16 (m, 1H), 7.05 (dt, J = 31.3, 7.2 Hz, 2H), 6.87 (s, 1H), 6.41 (s, 1H), 6.13 (d, J = 7.8 Hz, 1H), 3.65 (dd, J = 60.1, 5.7 Hz, 3H), 2.85 (m, J = 20.5, 14.8, 6.4 Hz, 2H), 2.45-2.18 (m, 2H), 1.80 (d, J = 37.7 Hz, 2H), 1.66-1.44 (m, 5H), 1.29-1.06 (m, 29H), 1.09 (d, J = 8.9 Hz, 3H), 0.81 (t, J = 6.7 Hz, 3H); 13C NMR (101 MHz, CDCl3) d 173.78 (s), 166.76 (s), 148.74 (s), 135.21 (s), 131.90 (s), 129.84 (s), 128.33 (s), 127.83 (s), 125.94 (s), 124.07 (s), 121.21 (d, J = 12.2 Hz), 118.53 (s), 117.27 (s), 110.92 (s), 110.35 (s), 59.08 (s), 47.86 (s), 47.55 (s), 32.38 (s), 31.87 (s), 31.56 (s), 30.90 (s), 28.79-28.15 (m), 24.76 (s), 24.46 (d, J = 4.5 Hz), 23.72 (d, J = 6.1 Hz), 21.67 (s), 13.10 (s); HRMS calcd. for C42H62N4O4 [M+Na+], 709.4663; found, 709.4667.
N-(2-(1H-Indol-3-yl)ethyl)-N-(2-(cyclohexylamino)-1-(3-nitrophenyl)-2-oxoethyl)stearamide (5h):
Yield: 63%; off-white solid; m.p. = 87-89°C; IR (neat): ?max = 3269 (NH str.), 1646 (Co str.), 1340 and 1535 (NO str.) cm-1; 1H NMR (400 MHz, CDCl3) d 8.21 (s, 1H), 8.07 (dd, J = 8.1, 1.7 Hz, 2H), 7.67 (s, 1H), 7.48-7.35 (m, 2H), 7.26 (d, J = 8.1 Hz, 1H), 7.07 (d, J = 32.7 Hz, 2H), 6.86 (d, J = 2.0 Hz, 1H), 6.51-6.40 (m, 1H), 5.79 (s, 1H), 3.84-3.75 (m, 1H), 3.64 (dd, J = 17.7, 10.0 Hz, 2H), 3.01-2.88 (m, 1H), 2.76-2.68 (m, 1H), 2.31 (dd, J = 9.5, 5.4 Hz, 2H), 1.86 (s, 2H), 1.78 (s, 1H), 1.69-1.48 (m, 7H), 1.36-1.24 (m, 3H), 1.20 (d, J = 18.0 Hz, 25H), 1.13-1.04 (m, 2H), 0.81 (t, J = 6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) d 174.9 (s), 168.2 (s), 148.2(s), 136.21 (s), 134.5 (s), 129.5 (s), 123.4 (s), 122.9 (s), 122.3 (s), 119.6 (s), 118.2 (s), 111.8 (s), 111.3 (s), 77.3 (s), 77.0 (s), 76.7 (s), 31.9 (s), 30.9 (s), 29.8 – 29.2 (m), 25.4 (s), 22.7 (s), 14.1 (s); HRMS calcd. for C42H62N4O4 [M+H+], 687.4844; found, 687.4847.

N-(2-(1H-Indol-3-yl)ethyl)-N-(2-(cyclohexylamino)-1-(4-nitrophenyl)-2-oxoethyl)stearamide (5i):
Yield: 62%; off-white solid; m.p. = 85-87 °C, IR (neat): ?max = 3290 (NH str.), 1615 (CO str.), 1342 and 1516 (NO str.) cm-1; 1H NMR (400 MHz, CDCl3) d 8.09 (t, J = 10.6 Hz, 3H), 7.48 (d, J = 8.3 Hz, 2H), 7.36 (d, J = 7.8 Hz, 1H), 7.25 (d, J = 8.1 Hz, 1H), 7.09 (d, J = 7.7 Hz, 1H), 7.03 (d, J = 7.5 Hz, 1H), 6.83 (s, 1H), 6.58-6.50 (m, 1H), 5.82 (s, 1H), 3.82-3.53 (m, 3H), 3.02-2.87 (m, 1H), 2.69 (dt, J = 14.6, 7.3 Hz, 1H), 2.38-2.20 (m, 4H), 1.90-1.78 (m, 2H), 1.56 (dd, J = 14.1, 6.9 Hz, 6H), 1.18 (s, 30H), 0.81 (s, 3H); 13C NMR (101 MHz, CDCl3) d 177.2 (s), 173.5 (s), 166.6 (s), 145.9 (s), 141.6 (s), 134.6 (s), 127.7 (s), 125.3 (s), 122.1 (s), 120.6 (d, J = 17.5 Hz), 118.0 (s), 116.6 (s), 110.2 (s), 109.7 (s), 61.3 (s), 47.0 (d, J = 5.8 Hz), 32.1 (d, J = 42.0 Hz), 31.1 (t, J = 11.4 Hz), 30.3 (s), 28.4-27.4 (m), 24. (s), 23.87 (s), 23.1 (d, J = 10.8 Hz), 21.1 (s), 12.5 (s); HRMS calcd. for C42H62N4O4 [M+K+], 725.4403; found, 725.4410.
Anti-quorum Sensing Study
The agar well diffusion assay was used to evaluate the anti-quorum sensing (anti-QS) activity of nine compounds synthesized via Ugi one pot reaction. The results showed that all nine compounds exhibited anti-QS activity. Out of which, 5b, 5c, and 5d, exhibited the most significant anti-QS activity (Table 1). The inhibition zones observed for these three compounds were larger than those observed for the other compounds tested. This finding is noteworthy as it suggests that these three compounds could be further studied and potentially developed into more potent anti-QS agents. Quorum sensing is a crucial process in bacterial communication and coordination, and interfering with this process can disrupt bacterial pathogenicity and virulence. Therefore, the anti-QS activity observed for these compounds suggests that they could be potential candidates for the development of novel anti-infective agents. In conclusion, the results of this study demonstrate the anti-QS activity of the compounds tested and highlight the potential of these compounds as anti-infective agents. Further studies are needed to determine the efficacy and safety of these compounds in vivo and to investigate their mechanism of action. We believe such findings of this study contribute to the growing body of research on anti-QS compounds and their potential applications in combating bacterial infections.
,CLAIMS:Claims:
I/We claim:
1.A process for preparing peptoids via Ugi reaction comprising:
(i) Tryptamine (1 mmol) was dissolved in methanol (2.5 mL) in a round-bottom flask of size 10 mL on a magnetic stirrer with 400 rpm for 15 minutes.
(ii) Then aldehyde (1mmol) was dissolved in methanol (2.5 mL) in a beaker. Under constant stirring of 400 rpm, the solution was poured into above reaction mixture with a syringe.
(iii) Then the solution (A) was stirred for 1 hour at 25 °C with 400 rpm stirring.
(iv) After that, stearic acid (1 mmol) was added to the reaction mixture under constant stirring of 400 rpm at 25 °C.
(v) Subsequently, cyclohexyl isocyanide (1 mmol) was added to the reaction mixture with a syringe with stirring speed of 400 rpm at 25 °C.
(vi) The reaction mixture was left overnight at 25 °C under constant stirring of 400 rpm.
(vii) Then, progress of reaction was monitored with the help of TLC. After completion of the reaction, solvents were dried under reduced pressure with the help of rotatory evaporator.
(viii) Afterwards, dichloromethane (10 mL) was added to the crude mixture and the organic layer was washed twice with saturated Na2CO3 solution.
(ix) After drying the organic layer over Na2SO4 (0.003 g), the solvent was removed in vacuo and the crude product was purified by column chromatography (EtOAc:Hexane; 3:7) and/or recrystallisation.

2.The compounds synthesized from the process of Claim (1) with structural formula (I) via Ugi four component reaction, procedure as claimed in claim 1, in which R is -C6H5, 4-CNC6H4, 4-CH3C6H4, 4-OCH3C6H4, 4-ClC6H4, 4-NMe2C6H4, 2-NO2C6H4, 3-NO2C6H4 and 4-NO2C6H4 and R’ is long aliphatic 18 carbon chain.

3.The compounds with structural formula-(I) as claimed in claim 2 act as anti-quroum sensing agents.