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.

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Hou YP, Sun J, Pang ZH, Lv PC, Li DD, Yan L, Zhang HJ, Zheng EX, Zhao J, Zhu HL

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. Epub 2011 Sep 1.

PubMed ID

21925884 [ View in PubMed

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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 muM for HEPG2 and IC(50)=0.93 muM 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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Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
TNP-470	Methionine aminopeptidase 2	IC 50 (nM)	1050	N/A	N/A	Details