Synthesis, structure-activity relationship and binding mode analysis of 4-thiazolidinone derivatives as novel inhibitors of human dihydroorotate dehydrogenase.

Reference

Zeng, T., Qi, Y., Li, X., Li, X., Li, X., Li, X., Zhu, Z., & Xu, Y.- ming. (2017). Synthesis, structure-activity relationship and binding mode analysis of 4-thiazolidinone derivatives as novel inhibitors of human dihydroorotate dehydrogenase. 8(6). https://doi.org/10.1039/c7md00081b

Abstract

A series of 4-thiazolidinone derivatives were synthesized and evaluated as novel human dihydroorotate dehydrogenase (DHODH) inhibitors. Compounds and displayed IC values of 1.75 and 1.12 μM, respectively. The structure-activity relationship was summarized. Further binding mode analysis revealed that compound could form a hydrogen bond with Tyr38 and a water-mediated hydrogen bond with Ala55, which may be necessary for maintaining the bioactivities of the compounds in this series. Further structural optimization of the - or -position of the phenyl group at R will lead to the identification of more potent DHODH inhibitors.