Facile synthesis of simple 2-oxindole-based compounds with promising antiproliferative activity

Discovery of novel potent anticancer agents with lower side effects is a challenge to overcome cancer, the second leading cause of death.

2-oxindole-based hydrazides (6a-g) and benzenesulfonyl hydrazides (9a-d) were synthesized by simple condensation reactions of the appropriate hydrazides (2a-g) or (8a-d) with 1-ethyl-2,3-oxindolinedione (4). They were screened for their cytotoxicity against HepG2 (liver), MCF-7 (breast), HCT116 (colon) and A549 (lung) cancer cell lines.

The substituted benzohydrazides (6b-g) revealed higher activity and selectivity toward the tested cell lines than doxorubicin and 9a-d. Compound 6c exhibited the highest activity against MCF-7 cell line with IC₅₀ = 0.0058 μM and it induced apoptosis by caspase-3 activation, Bax upregulation and Bcl-2 downregulation in a dose-dependent manner.

This compound can be considered as a potent cytotoxic agent with apoptotic induction property.