2. Academic Validation
  3. Potent Antitumor Activities and Structure Basis of the Chiral β-Lactam Bridged Analogue of Combretastatin A-4 Binding to Tubulin

Potent Antitumor Activities and Structure Basis of the Chiral β-Lactam Bridged Analogue of Combretastatin A-4 Binding to Tubulin

  • J Med Chem. 2016 Nov 23;59(22):10329-10334. doi: 10.1021/acs.jmedchem.6b01268.
Pengfei Zhou 1,  Yan Liu 2,  Lu Zhou 1,  Kongkai Zhu 2,  Kechang Feng 1,  Hao Zhang 2,  Yuru Liang 1,  Hualiang Jiang 2,  Cheng Luo 2,  Mingming Liu 1,  Yang Wang 1
Affiliations

Affiliations

  • 1 School of Pharmacy, Fudan University , Shanghai 201203, China.
  • 2 Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
PMID: 27805821 DOI: 10.1021/acs.jmedchem.6b01268
Abstract

A series of chiral β-lactam bridged analogues (3-substituted 1,4-diaryl-2-azetidinones) of combretastatin A-4 (CA-4) were synthesized asymmetrically, and their antitumor activities were evaluated in vitro and in vivo. The cocrystal structure of tubulin in complex with compound 9 was determined by X-ray crystallography, which showed that 9 binds to the same site as colchicine with similar binding mode, and the absolute configuration of its C-4 was first identified and demonstrated to be critically important for their antiproliferative activities.

Figures
Products