Synthesis and In Vitro Evaluation of Some Isatin-Thiazolidinone Hybrid Analogues as Anti-Proliferative Agents

P.      K. Ramshid; Sankar      Jagadeeshan; Anand      Krishnan; Mary      Mathew; S.      Asha Nair; M.      Radhakrishna Pillai

Abstract

A range of isatin-thiazolidinone hybrid analogues were synthesized and their cytotoxicity was evaluated against several cancer cell lines in vitro. The acute toxicity studies in mice models revealed that these analogues possess low systemic toxicity and are safe up to 1600mg/Kg. Among the compounds synthesized, 5-(2-nitrobenzylidene)-2-(isatin-3- azino)-thiazolidin-4-one (CI) has been shown to be the most active, highly promising compound which induced S phase arrest in cell cycle in a time dependent manner. Our initial analysis indicate that incorporation of electron withdrawing group at ortho position of the ring favors over the meta and para positions for eliciting its cytostatic effect. Overall, the in vitro biological evaluation suggests that the growth inhibitory effect of CI is promising and can be studied further.

Keywords: Isatin, thiazolidinone, cancer, cytotoxicity, cell cycle arrest, Isatin-Thiazolidinone Hybrid, Anti-Proliferative Agents, Phosphorylation, threonine, Alzheimer's, anti-proliferative effects, tyrosine kinases, p-glycoprotein, mitochondria, spectrophotometer, tetramethylsilane (TMS), DMEM, DMSO, 3-Thiosemicarbazone, 5-(2-Nitrobenzylidene), 4-Fluorobenzylidene, 4-Hydroxybenzylidene, isopropyl alcohol, ELISA microplate reader, cyclocondensation, NCI ADR Res, benzylidene ring, pharmacological screening, Trivandrum