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

( 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, 1 H NMR, 13 C 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 micromo-lar concentration (IC50, 2.52-7.41 mu M). The compound MeOIstDmMor was found G0/G1 cell cycle arrest in A431 cells and inhibited C-Jun, ,B-catenin, Akt proteins involve in cell proliferation. Among the four compounds, compound MeOIstDmMor exhibited strong anticancer potency in A549 (IC50, 2.52 mu M) than rest of the compounds. Similarly, compound MeOIstMor exhibited high anticancer activity in MCF-7, IC50; 2.93 mu M. (c) 2022 Elsevier B.V. All rights reserved.

Automated summary

In this study, four compounds were synthesized and characterized. Molecular docking studies revealed strong interaction between one compound and VEGFR2. In vitro experiments showed significant anticancer activity of these compounds against breast cancer, skin cancer, and lung cancer. One compound exhibited the strongest anticancer activity in A549 cells, while another compound showed high activity in MCF-7 cells.