New chalcones bearing isatin scaffold: synthesis, molecular modeling and biological evaluation as anticancer agents

Derivatives of isatin have been reported to possess cytotoxic effects against different human carcinoma cell lines. A series of new isatin-linked chalcones was synthesized starting from isatin. Most of the newly synthesized compounds were screened for their in vitro anticancer activity against human breast (MCF-7), liver (HepG-2), and colon (HCT-116) cancer cell lines. All the tested compounds exhibited antitumor activity, with IC50 ranging from 2.88 to 62.88 mu M in comparison to the reference drug used in this study, Imatinib. Compounds 2-5 were the most active, with IC50 ranging from 2.88 to 18.12 mu M for the three cell lines, while compound 7b also showed moderate activity against HepG-2, MCF-7 and HCT-116 with IC50 13.95, 31.66 and 11.78 mu M, respectively. Furthermore, compound 7d showed high activity against HepG-2 cells with IC50 12.84 mu M. Compound 4 was shown to be the most potent against both HepG-2 and HCT-116 cell lines, while compound 2 is the most potent against MCF-7. The compounds were also screened for their cytotoxic activity against normal breast cell line MCF-12A, and were found to possess mild cytotoxicity. A docking study was performed for the most active compounds in this study, 2-5, inside the active site of CDK2. All the docked compounds have shown favorable binding interactions and energy scores. Compound 4 has proved to be the best in binding interactions and energy score. These findings may explain the cytotoxic activity of the target compounds. A novel series of isatin-linked chalcones was synthesized. The target compounds were evaluated for their cytotoxic activity towards human breast (MCF-7), liver (HepG-2), colon (HCT-116) cancer cell lines and (MCF-12A) normal breast cell line. [GRAPHICS] .