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

Abstract

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 μM 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 μM 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 μM, respectively. Furthermore, compound 7d showed high activity against HepG-2 cells with IC50 12.84 μM. 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.