Design, Synthesis, Cytotoxicity, and Molecular Docking of New Thiazole Linked Tetrahydropyridine: Pyridine Hybrids

Cancer is a serious health issue that has affected people of all ages and everywhere for a long time. In view of it a library of thiazole—tetrahydropyridine—pyridine derivatives synthesized evaluated for their in vitro anticancer activity against human breast adenocarcinoma (MCF-7) and human lung cancer (A-549) cell lines, using Doxorubicin as the standard reference. The compound 6k with -F and -CH3 substituents found to be more potent with IC50 value of 8.72 ± 0.88 µM and 8.54 ± 0.85 µM against MCF-7 and A-549 cells, respectively, compound 6c containing trifluoromethoxy group as substituent with IC50 value of 9.45 ± 1.02 µM (MCF-7) and 9.59 ± 1.08 µM (A-549), compound 6 g with trifluoromethyl and methyl substituents presented prominent activity with IC50 value of 11.19 ± 1.03 µM (MCF-7) and 11.34 ± 1.07 µM (A-549) and compound 6 m with trifluoromethyl group showed good activity with IC50 value of 14.54 ± 1.03 µM (MCF-7) and 14.35 ± 1.05 µM (A-549). The toxicity test against Hek-293 revealed that they are not harmful to normal cells. Molecular docking study of potent ligand 6k revealed their best dock score and promising binding interactions. Presented ADME prediction of all compounds.