Abstract
Quinoline derivatives have been reported to possess multi-therapeutic potential owing to the manifestations of different pharmacological effects. The current research work describes about the design and synthesis of a series of novel benzoquinoline analogues with an objective to evaluate their antiproliferative structure-activity relationship against colon, breast and hepatocellular cancers. Upon synthesis, all derivatives' chemical structures were elucidated through FTIR, (HNMR)-H-1 and (CNMR)-C-13 spectroscopic analysis. All derivatives were investigated for their in vitro anti-proliferative property against three different cancer cell lines (viz., colon carcinoma HT29, Caucasian breast adenocarcinoma MCF7, hepatocellular carcinoma HepG2) and a normal non-transformed human foreskin fibroblast Hs27 cell line. All derivatives demonstrated varied degrees of strong anticancer effect against all of the cell lines with the 2-Amino-4-(4-nitrophenyl)-5,6-dihydrobenzo[h]quinoline-3-carbonitrile (CNMP, 2) exhibited the most potent antiproliferative effect viz. LC50 21.23 mu M for breast, 8.24 mu M for colon, and 26.15 mu M for the hepatocellular, respectively. Molecular docking studies against all the the target crystal structures of cancer proteins (1HK7, 3EQM, 3IG7 and 4FM9) revealed significant binding affinities via hydrophobic and H-bonding interactions with all the compounds in conformity with the wet lab results. CNMP showed the highest binding energy of -7.55 in the HT29, -6.9 (both in MCF7 HepG2) kcal/mol. Based on the results obtained from wet lab and dry lab experiments, it can be proposed that CNMP might prove to be a potential lead structure for the design and synthesis of more potent anticancer candidates. (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.