Optimization of 2-(3-(arylalkyl amino carbonyl) phenyl)-3-(2-methoxyphenyl)-4-thiazolidinone derivatives as potent antitumor growth and metastasis agents

• Design, synthesis and optimization of a novel series of 2,3-diaryl-4-thiazolidinones.
• The structure–activity relationship toward cancer cells proliferation was discussed.
• Several compounds displayed excellent inhibitory activities on migration.
• Compound 39 suppressed tumor growth and metastasis as well as promoted survival rate.

A series of 2,3-diaryl-4-thiazolidinone derivatives were synthesized and evaluated for their antiproliferative properties against two well-known cancer cell lines (A549 as human lung cancer and MDA-MB-231 as human breast cancer). Structure activity relationship (SAR) analysis resulted in the discovery of 2-(3-(arylalkyl amino carbonyl)phenyl)-3-(2-methoxy-phenyl)-4-thiazolidinone derivatives with high potent inhibitory effects on the proliferation of both cancer cell lines. Furthermore, several compounds with potent antiproliferative activities displayed excellent inhibitory activities on migration with an IC50 of about 0.05 μM on MDA-MB-231 cells in two different migration assays. In particular, compound 39 was indicated to suppress tumor growth and metastasis as well as promote survival rate. Intriguingly, this series of analogs have been indicated to inhibit tumor cell proliferation through inducing cell cycle arrest. These results suggested that the new series of 2-(3-(arylalkyl amino carbonyl)phenyl)-3-(2-methoxyphenyl)-4-thiazolidinone derivatives could be regarded and developed as novel highly potential anticancer agents in the future.

SAR analysis resulted in the discovery of novel 2,3-diaryl-4-thiazolidinones with potent antiproliferation and antimigration on both cancer cell lines, which suppressed tumor growth and metastasis as well as promoted survival.Figure optionsDownload as PowerPoint slide