Biological activity and molecular docking studies of some new quinolines as potent anticancer agents

The objective of this study is to investigate the antiproliferative and cytotoxic properties and the action mechanism of substituted quinoline and tetrahydroquinolines 3, 4, 5, 7, and 8 against rat glioblastoma (C6), human cervical cancer (HeLa), human adenocarcinoma (HT29) cancer cell lines by BrdU Cell Proliferation ELISA, Lactate Dehydrogenase, DNA laddering and Topoisomerase I assays. The results of the study showed that 6,8-dibromotetrahydroquinoline 3 possess in vitro antiproliferative activity against C6, HeLa, and HT29 cell lines while morpholine/piperazine substituted quinoline 7 and 8 showed selective antiproliferative activity on C6 cell line with IC50 values 47.5 and 46.3 mu g/mL, respectively. Moreover, 6,8-dibromoTHQ 3 caused DNA fragmentation while it did not inhibit the Topoisomerase I (Topo I) enzyme. On the other hand, compound 8 did not cause DNA laddering while 8 inhibited the Topo I enzyme. According to these results, 6,8-dibromoTHQ 3 stimulates apoptosis on the C6 cell line while 6,8-dibromo-3-morhonilylquinoline (8) inhibits the Topo I enzyme to cause antiproliferative activity. Graphic abstract

Automated summary

This study investigated the antiproliferative properties of substituted quinoline and tetrahydroquinolines against different cancer cell lines, finding that 6,8-dibromotetrahydroquinoline 3 showed activity against all tested cell lines while morpholine/piperazine substituted quinoline 7 and 8 exhibited selective antiproliferative activity. Additionally, compound 3 caused DNA fragmentation, compound 8 inhibited Topoisomerase I enzyme activity, and the different compounds had varying effects on apoptosis and antiproliferative mechanisms.