Synthesis, cytotoxicity, and molecular docking studies of novel selenourea-embedded quinoline and benzimidazole derivatives against MDA-MB-231 and A549 cancer cell lines

Development of hybrid molecules has been broadly considered one of the promising strategies towards cancer treatment owing to their unique modes of action on various cell lines. Herein, we describe the synthesis of novel libraries of selenourea-heterocyclic amine hybrids and their in vitro anticancer activities against MDA-MB-231 (breast cancer) and A549 (lung cancer) targets. A selenourea moiety was merged with two distinct heterocyclic amines: 5-(piperazin-1-ylmethyl) quinolin-8-ol (series-1) and 2-(piperazin-1-yl)-1H-benzo[d]imidazole (series-2). A total of 18 derivatives were synthesized and fully characterized using NMR, FT-IR, and Mass spectrometry. Preliminary in vitro anticancer activity evaluation revealed that few selenourea derivatives exhibited significant potency. Among the tested compounds, 18e from series-2 displayed the most potent activity against triple-negative MDA-MB-231 invasive ductal carcinoma breast cancer cells (IC?? =13.9 ?M), whereas 18f emerged as the most potent against the human lung carcinoma (A549) cell lines with an IC?? value of 17.6 ?M. In series-1, 17i showed notable efficacy against A549 cells (IC?? =22.5 ?M) and invasive ductal carcinoma breast cancer cells MDA-MB-231 (IC?? =37.9 ?M). Morphological changes in MDA-MB-231 cells upon treatment with 18e, 18d and 18f were investigated by light microscopy analysis. The differential binding free energy (??G) was used to compare the relative binding strengths of compound 18e with the reference ligands. Negative ??G values for NR3C1 (1.66 kcal/mol) and MAPK8 (0.52 kcal/mol) indicated stronger interactions and enhanced complex stability, whereas moderate positive values for STAT3, MAPK1, and BCL2L1 suggested promising but comparatively weaker affinities relative to the controls