Anticancer potency of N(4)-ring incorporated-5-methoxyisatin thiosemicarbazones

•Isatin thiosemicarbazones exhibited prominent anti-proliferative activity toward MCF-7, A549 and A431 cell lines.•Substitution of methoxy group on the fifth position of isatin and ring on N(4) position of thiosemicarbazone influenced the anticancer potency.•Single crystal X-ray study confirmed the existence of thiosemicarbazones in thione tautomeric form with intra and intermolecular H-bondings.•Molecular docking studies showed that compound interacted strongly with VEGFR2 via hydrogen bonding.•The compound was found G0/G1 cell cycle arrest in A431 cells and inhibited C-Jun, β-catenin, akt proteins involved in cell proliferation. (Z)-N'-(5-methoxy-2-oxoindolin-3-ylidene)thiomorpholine-4-carbothiohydrazide (MeOIstTmor), (Z)-N'-(5-methoxy-2-oxoindolin-3-ylidene)-2,6-dimethylmorpholine-4-carbothiohydrazide (MeOIstDmMor), (Z)-N'-(5-methoxy-2-oxoindolin-3-ylidene)morpholine-4-carbothiohydrazide (MeOIstMor) and (Z)-2-(5-methoxy-2-oxoindolin-3-ylidene)-N,N-dimethylhydrazine-1-carbothioamide (MeOIstDm) were synthesized and characterized by elemental analysis, FT-IR, 1H NMR, 13C NMR, UV–Vis, ESI-HRMS and single crystal X-ray analysis. Molecular docking studies showed that compound MeOIstDmMor interacted strongly with VEGFR2 via hydrogen bonding. The anticancer activities of the synthesized compounds were tested against breast cancer (MCF-7), skin cancer (A431), and lung cancer (A549) for cell viability, cell cycle arrest and western blot analysis. The compounds exhibited significant anticancer potency in micromolar concentration (IC50, 2.52–7.41 µM). The compound MeOIstDmMor was found G0/G1 cell cycle arrest in A431 cells and inhibited C-Jun, β-catenin, Akt proteins involve in cell proliferation. Among the four compounds, compound MeOIstDmMor exhibited strong anticancer potency in A549 (IC50, 2.52 µM) than rest of the compounds. Similarly, compound MeOIstMor exhibited high anticancer activity in MCF-7, IC50; 2.93 µM.