Synthesis and cytotoxic activity of 1,5,6,7-tetrahydroindol-4-one derivatives and its thio analogue

Abstract

Derivatives of 1,5,6,7-tetrahydroindol-4-one and its thio analogue were synthesized and their cytotoxicity against HEK293, Jurkat and MCF-7 cells was investigated in vitro. The hit compound, 6,6-dimethyl-1-(2-methylphenyl)-2-phenyl-1,5,6,7-tetrahydro-4H-indol-4-one, was found to inhibit the metabolic activity of lymphoblastic leukemia cells (Jurkat) with IC50 = 14.8 µM and normal human embryonic kidney cells (HEK293) with IC50 = 93.63 µM. The proposed mechanism of cytotoxic action of the most active compound was shown in silico to be mediated by interaction with the cyclin-dependent kinase CDK9 site.