2. Academic Validation
  3. Antimitotic and vascular disrupting agents: 2-hydroxy-3,4,5-trimethoxybenzophenones

Antimitotic and vascular disrupting agents: 2-hydroxy-3,4,5-trimethoxybenzophenones

  • Eur J Med Chem. 2014 Apr 22:77:306-14. doi: 10.1016/j.ejmech.2014.02.061.
Chih-Yi Chang 1,  Hsun-Yueh Chuang 1,  Hsueh-Yun Lee 1,  Teng-Kuang Yeh 2,  Ching-Chuan Kuo 2,  Chi-Yen Chang 3,  Jang-Yang Chang 4,  Jing-Ping Liou 5
Affiliations

Affiliations

  • 1 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan, ROC.
  • 2 Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli 350, Taiwan, ROC.
  • 3 National Institute of Cancer Research, National Health Research Institutes, Tainan 70456, Taiwan, ROC.
  • 4 National Institute of Cancer Research, National Health Research Institutes, Tainan 70456, Taiwan, ROC; Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC. Electronic address: jychang@nhri.org.tw.
  • 5 School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan, ROC; School of Pharmacy, National Defense Medical Center, 161 Minchuan East Road, Section 6, Taipei 114, Taiwan, ROC. Electronic address: jpl@tmu.edu.tw.
PMID: 24657567 DOI: 10.1016/j.ejmech.2014.02.061
Abstract

2-Hydroxy-3,4,5-trimethoxybenzophenones (8-16) manifest pseudo-ring formation involving intramolecular hydrogen bonding of the 2-OH and the carbonyl group. Among the synthetic products described in this report, (3-hydroxy-4-methoxyphenyl)(2-hydroxy-3,4,5-trimethoxyphenyl)-methanone (14) and (3-amino-4-methoxyphenyl)(2-hydroxy-3,4,5-trimethoxy-phenyl)methanone (16) exhibit significant antiproliferative activity against KB cells with IC50 values of 11.1 and 11.3 nM, respectively. These two compounds also displayed tubulin affinity comparable to that of combretastatin A-4. In studies with human umbilical vein endothelial cells, compounds 14 and 16 revealed concentration-dependent vascular-disrupting properties. The results support the rationale of the pseudo-ring concept and suggest further investigation of A-ring modification in these benzophenones.

Keywords

Antiproliferative; CA-4; Vascular-disrupting agents.

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