Synthesis, cytotoxicity, Pan-HDAC inhibitory activity and docking study of new N-(2-aminophenyl)-2-methylquinoline-4-carboxamide and (E)-N-(2-aminophenyl)-2-styrylquinoline-4-carboxamide derivatives as anticancer agents

In this study, new cytotoxic agents based on 2-aminobenzamide scaffold were designed, synthesized and evaluated against A549, HCT116 and HT-29 cancer cell lines (inhib%) in doses of 5  μM and 20 μM that displayed moderate to good effects. The synthesized compounds were evaluated for their inhibitory activity (inhib%) against Pan-HDAC on HCT116 and HT-29 cell lines which displayed inhibitory activity (%) of 0–67.34% on HT-29 and 5.67–50.18% on HCT116 cell line at concent rations of 100 μM. Generally, Pan-HDAC inhibitory activity (inhib%) in (E)-N-(2-aminophenyl)-2-styrylquinoline-4-carboxamide series was better than N-(2-aminophenyl)-2-methylquinoline-4-carboxamide series. The most potent compounds7h,7i, 8b,8c,8l and8j were selected to determine IC50 values. Interestingly, the most cytotoxicity was calculated for small size molecules of7h and7i from N-(2-aminophenyl)-2-methylquinoline-4-carboxamide series, 2.4  μM (HCT116) and 6.4 μM (HT-29) for compound7h and 5.2  μM (HCT116) and 10.65 μM (HT-29) for compound7i. Compound8j (5.8  μM) and compound8l (8.5  μM) from (E)-N-(2-aminophenyl)-2-styrylquinoline-4-carboxamide series displayed the most cytotoxicity on HCT116 cell line. Docking study of selected compounds7h,7i, 8b,8c,8l, and8j was performed on HDAC isoforms that exhibited the best docking scores on sirtuins. Generally, predicted ADME properties for synthesized compounds with the pkCSM web-tool were appropriate. Based on Molinspiration Calcul...
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research