“…According to the analysis of the docking results, the promised compounds were synthesized using the available methods in organic chemistry previously published by us (Scheme 1) [42,45 ].…”
The present study explores the potential of the new sulfonamide derivatives coupled with salicylamide or anisamide scaffold as immune checkpoint PD-L1 inhibitors. Based on in silico virtual screening 32 derivatives were synthesized and tested in vitro as PD-L1 inhibitors using screening ELISA assay. Five compounds gave promised results with more than 50% inhibition. The most active, with activity 57.152%, was 5-Chloro-N-( 4-(N-(3uorophenyl)sulfamoyl)phenethyl)salicylamide (30). The other compounds were 5-Chloro-2-methoxy-N-(4-(N-(4-uorophenyl)sulfamoyl)benzyl)benzamide (4, 53.327%), 5-Chloro-2-methoxy-N-(4-(N-(4-methylphenyl)sulfamoyl)phenethyl)benzamide (17, 51.253%), 5-Chloro-N-(4-(N-(4-(tri uoromethyl)phenyl)sulfamoyl)phenethyl)salicylamide (31, 51.058%) and 5-Chloro-2-methoxy-N-(4-(N-(2,4-di uorophenyl)sulfamoyl)benzyl)benzamide (7, 50.993). All compounds were found to be safe and have no cytotoxic effect against the broblast cell lines. Moreover, compound 4, 7,17, and 30 should no or little anti-proliferative activity against the cell lines use in this study except compound 4, which have anti-proliferative activity against PC-3 (66.640%). On the other hand, compound 31 should remark activities against the cell lines MCF7, DU-145, and PC-3. In general, human prostate cancer cell line PC-3 is highly sensitive towards some of the 32 compounds tested at 10 μmol. The molecular docking study and ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis of the bioactive compounds were used to elucidate the mode-of-action mechanism.
“…Sulfonamides consist of major drug components called sulfa drugs. The functional group -SO 2 NH 2 in sulfonamides enables it to possess many pharmacological properties such as antibacterial (Qadir et al, 2015), antifungal (Jyothi and Madhavi, 2018), antimalarial (Maloy Kumar et al, 2018), anticancer (Abdelaziz et al, 2015), inhibitors of human carbonic anhydrase I (hCA I) and human carbonic anhydrase II (hCA II, Kilicaslan et al, 2016), anti-HIV (Jiao et al, 2010), and many others. Carboxamides are also ubiquitous functionality GRAPHICAL ABSTRACT | in medicate particles as pharmacophores (Montalbetti and Falque, 2005).…”
The increase of antimicrobial resistance (AMR) and antimalarial resistance are complex and severe health issues today, as many microbial strains have become resistant to market drugs. The choice for the synthesis of new dipeptide-carboxamide derivatives is as a result of their wide biological properties such as antimicrobial, anti-inflammatory, and antioxidant activities. The condensation reaction of substituted benzenesulphonamoyl pentanamides with the carboxamide derivatives using peptide coupling reagents gave targeted products (8a-j). The in silico antimalarial and antibacterial studies showed good interactions of the compounds with target protein residues and a higher dock score in comparison with standard drugs. In the in vivo study, compound 8j was the most potent antimalarial agent with 61.90% inhibition comparable with 67% inhibition for Artemisinin. In the in vitro antimicrobial activity, compounds 8a and 8b (MIC 1.2 × 10−3 M and 1.1 × 10−3 M) were most potent against S. aureus; compound 8a, 8b, and 8j with MIC 6.0 × 10−3 M, 5.7 × 10−4 M, and 6.5 × 10−4 M, respectively, were the most active against B. subtilis; compound 8b (MIC 9.5 × 10−4 M) was most active against E.coli while 8a, 8b and 8d were the most active against S. typhi. Compounds 8c and 8h (MIC 1.3 × 10−3 M) each were the most active against C. albicans, while compound 8b (MIC 1.3 × 10−4 M) was most active against A. niger.
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