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

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)138-142
Number of pages5
JournalVascular Pharmacology
Volume48
Issue number2-3
DOIs
Publication statusPublished - Feb 2008

Fingerprint

Umbilicus
Endothelial Cells
Phenytoin
Cell Cycle
Cyclin-Dependent Kinase 2
Structure-Activity Relationship
Sulfur
Human Activities
Anticonvulsants
Cell Count
Cell Proliferation
DNA
diphenylthiohydantoin
Proteins

Keywords

  • Angiogenesis
  • Capillary-like tube formation
  • DPTH
  • Endothelial cells
  • p21

ASJC Scopus subject areas

  • Pharmacology

Cite this

Structure and anti-proliferation function of 5,5-diphenyl-2-thiohydantoin (DPTH) derivatives in vascular endothelial cells. / Cheng, Cheng Kuo; Wu, Jender; Liu, Yuan; Lee, Tong Sheng; Kang, Shuo Jhen; Sheu, Ming Thau; Lee, Wen Sen.

In: Vascular Pharmacology, Vol. 48, No. 2-3, 02.2008, p. 138-142.

Research output: Contribution to journalArticle

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