Antiproliferative Evaluation and Molecular Docking studies of some Sulfonyl-α-L-amino acid Derivatives coupled with Anisamide Scaffold

A series of sulfonyl-α-L-amino acid derivatives coupled with anisamide scaffold, previously synthesized, were evaluated in vitro for their antiproliferative activity against human cell lines namely, Caucasian breast adenocarcinoma (MCF7), hepatocellular carcinoma (HEPG2), Colon cell line (HCT116), and pancreatic cell line (PaCa2) and comparing their results with skin fibroblast cell line (BJ1) as a normal cell line, using MTT cell proliferation assay. The results showed that 2-(4-{[(5-Chloro-2-methoxy-benzoyl)amino]methyl}phenyl)sulfonyl-L-cysteine (5), 2-(4-{[(5-Chloro-2-methoxy-benzoyl)amino]methyl}phen-yl)sulfonyl-L-glutamine (14), and 2-(4-{[(5-Chloro-2-methoxy-benzoyl)amino]methyl}phenyl)sulfonyl-L-tryptophan (18) were the most active molecules against HEPG2, MCF7, and PaCa2 cell lines with IC50 51.9, 54.2, and 59.7 µg/ml respectively. On contrary, 2-(4-{[(5-Chloro-2-methoxy-benzoyl)amino]methyl}phenyl)sulfonyl-L-valine (3) has a high selectivity index for (MCF7) and (PaCa2) cell lines at, IC50 90.9 and 69.5 µg/ml, respectively. Similarly, 2-(4-{[(5-Chloro-2-methoxy-benzoyl)-amino]methyl}phenyl)sulfonyl-L-glycine (1) and 2-(4-{[(5-Chloro-2-methoxy-benzoyl)amino]methyl}phenyl)sulfonyl-L-lysine (10) have cytotoxic selectivity towards (HEPG2) cell line with a high selectivity index with IC50 85.1 and 87.0 µg/ml, respectively. Moreover, a docking study was performed to predict the correct binding geometry for each binder and compare it with its activity.