1. Academic Validation
  2. Synthesis and antitumor activity of 1,2,4-triazoles having 1,4-benzodioxan fragment as a novel class of potent methionine aminopeptidase type II inhibitors

Synthesis and antitumor activity of 1,2,4-triazoles having 1,4-benzodioxan fragment as a novel class of potent methionine aminopeptidase type II inhibitors

  • Bioorg Med Chem. 2011 Oct 15;19(20):5948-54. doi: 10.1016/j.bmc.2011.08.063.
Ya-Ping Hou 1 Juan Sun Zhong-Hua Pang Peng-Cheng Lv Dong-Dong Li Li Yan Hong-Jia Zhang Emily Xi Zheng Jing Zhao Hai-Liang Zhu
Affiliations

Affiliation

  • 1 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
Abstract

A series of 1,2,4-triazole derivatives containing 1,4-benzodioxan (5a-5q) have been designed, synthesized, structurally determined, and their biological activities were evaluated as potential MetAP2 inhibitors. All the synthesized compounds were first reported. Among the compounds, compound 5k showed the most potent biological activity against HEPG2 Cancer cell line (IC(50)=0.81 μM for HEPG2 and IC(50)=0.93 μM for MetAP2), which was comparable to the positive control. Docking simulation by positioning compound 5k into the MetAP2 structure active site was performed to explore the possible binding model. The results of Apoptosis and Western-blot assay demonstrated that compound 5k possessed good antitumor activity against HEPG2 Cancer cell line. Therefore, compound 5k with potent inhibitory activity in tumor growth inhibition may be a potential antitumor agent against HEPG2 Cancer cell.

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