Design and synthesis of 2-iminothiazolidin-4-one moiety-containing compounds as potent antiproliferative agents.

A new series of 2,5-diaryliminothiazolidin-4-ones were designed and synthesized as potent antiproliferative agents. The antiproliferative activities of the 25 target compounds were evaluated against three cancer cell lines (A549, H460 and HT29) by MTT assay. Pharmacological data indicated that most of the compounds possessed moderate activity, some showed remarkable activity against one or more cell lines. As the most promising compound, 8s (with IC(50) values of 1.1, 0.01 and 1.3 µM against the A549, H460 and HT29 cell lines) was 1.1- to 270-fold more potent than the reference drug sorafenib. Furthermore, preliminary structure-activity relationships (SARs) were summarized to provide guidance for further design and discovery of 2-iminothiazolidin-4-one-based antiproliferative agents.