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

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Cancer Biology

Background:

• Quinoline and tetrahydroquinoline scaffolds are recognized for their diverse biological activities.
• Developing novel anticancer agents with distinct mechanisms of action is crucial for overcoming drug resistance.

Purpose of the Study:

• To evaluate the antiproliferative and cytotoxic effects of novel substituted quinoline and tetrahydroquinoline derivatives.
• To elucidate the mechanisms of action, including apoptosis induction and enzyme inhibition, of active compounds.

Main Methods:

• In vitro screening against C6 (glioblastoma), HeLa (cervical), and HT29 (adenocarcinoma) cancer cell lines.
• Assays employed: BrdU Cell Proliferation ELISA, Lactate Dehydrogenase assay, DNA laddering, and Topoisomerase I inhibition assay.

Main Results:

• 6,8-dibromotetrahydroquinoline (3) demonstrated in vitro antiproliferative activity against all tested cell lines.
• Morpholine/piperazine substituted quinolines (7 and 8) exhibited selective antiproliferative activity against C6 cells (IC50 values 47.5 and 46.3 µg/mL).
• Compound 3 induced DNA fragmentation (apoptosis), while compound 8 inhibited Topoisomerase I activity without causing DNA laddering.

Conclusions:

• 6,8-dibromotetrahydroquinoline (3) acts as an apoptosis-inducing agent against C6 cells.
• 6,8-dibromo-3-morhonilylquinoline (8) exerts its antiproliferative effect by inhibiting Topoisomerase I.
• These findings highlight the potential of these quinoline derivatives as leads for anticancer drug development.