2-(Thienothiazolylimino)-1,3-thiazolidin-4-ones inhibit cell division cycle 25 A phosphatase.

Cell division cycle dual phosphatases (CDC25) are essential enzymes that regulate cell progression in cell cycle. Three isoforms exist as CDC25A, B and C. Over-expression of each CDC25 enzyme is found in cancers of diverse origins. Thiazolidinone derivatives have been reported to display anti-proliferative activities, bactericidal activities and to reduce inflammation process. New 2-(thienothiazolylimino)-1,3-thiazolidin-4-ones were synthesized and evaluated as inhibitors of CDC25 phosphatase. Among the molecules tested, compound 6 inhibited CDC25A with an IC50 estimated at 6.2±1.0µM. The binding of thiazolidinone derivative 6 onto CDC25A protein was reversible. In cellulo, compound 6 treatment led to MCF7 and MDA-MB-231 cell growth arrest. To our knowledge, it is the first time that such 4-thiazolidinone derivatives are characterized as CDC25 potential inhibitor.

Synthesis and biological evaluation of novel 2-heteroarylimino-1,3-thiazolidin-4-ones as potential anti-tumor agents.

A series of 35 heteroarylimino-1,3-thiazolidinones with three sites of functionalization were synthesized and their antiproliferative properties were studied. The in vitro screening by MTT assay was performed against five cancer cell lines (human colon cancer cell lines HT29, HCT116 and SW620 and breast cancer cell lines MCF7 and MDA-MB-231). It was observed that N3-substituted thiazolidinones had moderate activities whereas 5-benzylidene thiazolidinones showed promising activities. To investigate the mechanism of action, detailed biological studies of six selected compounds (those presenting the lower mitotic index) were carried out on the human colon cancer HT29 cell line. Cell cycle assay revealed that those compounds induced cell accumulation in G2/M and in subG0/G1 phases of cell cycle. Moreover, dissipation of mitochondria membrane potential was observed as well as redox changes in treated cells.