Exploring tetrahydroquinoline Derivatives: A New Frontier in Cancer Treatment

Tetrahydroquinoline derivatives are emerging as promising anticancer agents due to their versatile biological activities. In this study, we designed, synthesized, and evaluated novel derivatives for anticancer potential. The compounds were synthesized via nitration, benzoylation, and reduction, achieving high yields and structural diversity. Molecular docking studies on the mTOR protein (PDB ID: 4JT6) revealed strong binding affinities, with key interactions at active site residues. MD simulations in GROMACS (50 ns) confirmed the stability of compound-protein complexes. In vitro cytotoxicity assays against A549, MDA-MB-231, and MCF-7 cancer cell lines showed potent activity, with UC-RS-04 displaying an IC50 of 0.027 µM in lung cancer, outperforming standard drugs like 5-Fluorouracil (0.28 µM) and Everolimus (0.09 µM). Toxicity studies on VERO cells confirmed selectivity, sparing normal cells. This multidisciplinary approach integrating synthetic chemistry, computational studies, and biological evaluation highlights the potential of tetrahydroquinoline derivatives as selective mTOR inhibitors with significant anticancer activity.

Publication History

Received: 27 February 2025

Accepted after revision: 28 April 2025

Accepted Manuscript online:
28 April 2025