Structure and anti-proliferation function of 5,5-diphenyl-2-thiohydantoin (DPTH) derivatives in vascular endothelial cells.

Cheng-Kuo Cheng, Jender Wu, Yuan Liu, Tong-Sheng Lee, Shuo-Jhen Kang, Ming-Thau Sheu, Wen-Sen Lee

Department of Ophthalmology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; Fu-Jen Catholic University, School of Medicine, Taipei, Taiwan.

Vascular pharmacology 2008 Feb-Mar

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Previously, we identified DPTH, an analogue of antiepileptic drug phenytoin (5,5-diphenylhydantoin, DPT), capable of retarding the cell cycle in the human vascular endothelial cells. Our data suggest that DPTH inhibits human umbilical venous endothelial cells (HUVEC) proliferation by increasing the level of p21 protein, which in turn inhibits the activities of cyclin-dependent kinase (CDK)2 and CDK4, and finally interrupts the cell cycle. To search chemicals with more potency in anti-angiogenic activity, we designed and synthesized several chemical compounds based on the structure-activity relationship consideration. We evaluated the anti-angiogenic activity of these compounds by examining their effects on DNA synthesis, cell number, p21 induction and capillary-like tube formation. Our results showed that introduction of side chain containing an aromatic ring structure with right spatial arrangement at sulfur atom of DPTH enhanced the anti-angiogenic activity in HUVEC.

Citation

Cheng-Kuo Cheng, Jender Wu, Yuan Liu, Tong-Sheng Lee, Shuo-Jhen Kang, Ming-Thau Sheu, Wen-Sen Lee. Structure and anti-proliferation function of 5,5-diphenyl-2-thiohydantoin (DPTH) derivatives in vascular endothelial cells. Vascular pharmacology. 2008 Feb-Mar;48(2-3):138-42