Synthesis, antiproliferative activity and docking study of novel rhodanine derivatives as Bcr-Abl T1351 inhibitors

Abstract

A series of novel N-substituted rhodanines 6a–g were synthesized by a microwave synthesizer, and evaluated for their anti-proliferative activity. Most of the compounds showed inhibition against K562 cells in a dose-dependent manner and in particular compounds 6a, 6b and 6f exhibited most potent activity with an IC50 value of 19.62, 24.01 and 22.91 µg/ml by MTT assay. Further in silico docking studies of the above compounds against Bcr-Abl T1351 protein showed good binding affinity, thus indicating that the compounds behave as third generation inhibitors. A dose-dependent increase in LDH release upon treatment with 6a–g complements the MTT assay for anti-proliferative activity. Flow cytometry of 6a showed that it interferes with the cell division by indicating G1 phase arrest followed by apoptosis.