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

• Published in: Medical oncology (Northwood, London, England) Vol. 38; no. 7; p. 84
• Main Authors: Köprülü, Tuğba Kul, Ökten, Salih, Atalay, Vildan Enisoğlu, Tekin, Şaban, Çakmak, Osman
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.07.2021; Springer Nature B.V
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Biological activity; Cancer therapies; Cell culture; Cell cycle; Cell growth; Cell Proliferation - drug effects; Cell Proliferation - physiology; Cervical cancer; Cytotoxicity; Dehydrogenases; Dose-Response Relationship, Drug; Enzymes; HeLa Cells; Hematology; HT29 Cells; Humans; Internal Medicine; Kinases; MCF-7 Cells; Medical research; Medicine; Medicine & Public Health; Metabolism; Metabolites; Metastasis; Molecular Docking Simulation - methods; Oncology; Original Paper; Pathology; Quinolines - chemistry; Quinolines - pharmacology; Quinoline; Cytotoxicity; Molecular docking; Anticancer activity; Tetrahydroquinoline
• ISSN: 1357-0560; 1559-131X
• DOI: 10.1007/s12032-021-01530-w

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 IC 50 values 47.5 and 46.3 µg/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