Synthesis, Anticancer Evaluation and DNA-Binding Spectroscopic Insights of Quinoline-Based 1,3,4-Oxadiazole-1,2,3-triazole Conjugates

The present work involves a pharmacophore hybridization strategy to combine key biologically active scaffolds. The study led to the synthesis of quinoline based oxadiazole-triazole conjugates with favorable physicochemical properties as anti-cancer agents. Among the synthesized compounds 8(a-p), in vitro screening against a panel of four cancer cell lines identified compound 8k, with o-chloro substitution on the phenyl ring, as potent against human lung carcinoma (A-549) cells (IC50 =5.6 mu M), while showing no significant cytotoxicity upto 200 mu M concentration in normal cells. Compound 8 k with o-chloro substitution induced nuclear morphological changes in A-549 cells as visualized by DAPI (4,6-diamidino-2-phenylindole) and was shown to bind firmly with A-T rich region in DNA. Changes in DNA topology studied through gel electrophoresis and groove mode of binding to ct-DNA through multi-spectroscopic techniques were observed, further validated by molecular docking studies. Overall, the study illustrates successful hybridization strategy leading to compound 8 k as promising anticancer agent for further structural optimization and biological evaluation.