Development of quinoline‑based 1,3,4-oxadiazole derivatives as in vitro anticancer agents targeting breast cancer cell lines

To synthesize and evaluate novel quinoline-1,3,4-oxadiazole hybrid derivatives as potential anticancer agents against breast cancer cell lines. The target derivatives were synthesized and characterized using spectroscopic techniques. Their in vitro anticancer activity was evaluated against MCF-7 and MDA-MB-231 breast cancer cell lines. Structure–activity relationships (SAR) were analyzed, and molecular docking was performed to investigate the binding interactions of the most active compound. Several derivatives exhibited promising anticancer activity. Compound 8f showed potent activity against MCF-7 cells (IC50 = 11.12 ± 1.32 μM), comparable to tamoxifen (IC50 = 11.3 ± 1.2 μM). SAR analysis suggested that electron-donating substituents on the aromatic phenyl ring generally enhanced activity, whereas electron-withdrawing groups produced variable effects depending on their substitution position. Molecular docking revealed a favorable binding orientation for compound 8f, with hydrogen-bond interactions involving Leu792 and Thr854. Quinoline-1,3,4-oxadiazole hybrids represent promising candidates for further anticancer research. Compound 8f warrants additional investigation, particularly for its potential against aggressive breast cancer subtypes, including triple-negative breast cancer (TNBC).