Abstract
m-AMSA, an established inhibitor of eukaryotic type II topoisomerases, exerts its cidal effect by binding to the enzyme-DNA complex thus inhibiting the DNA religation step. The molecule and its analogues have been successfully used as chemotherapeutic agents against different forms of cancer. After virtual screening using a homology model of the Mycobacterium tuberculosis topoisomerase I, we identified m-AMSA as a high scoring hit. We demonstrate that m-AMSA can inhibit the DNA relaxation activity of topoisomerase I from M. tuberculosis and Mycobacterium smegmatis. In a whole cell assay, m-AMSA inhibited the growth of both the mycobacteria.
Keywords:
Mycobacterium tuberculosis; Topoisomerase inhibitors; Type I topoisomerase; m-AMSA.
Copyright © 2014 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amsacrine / chemistry
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Amsacrine / pharmacology*
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Antitubercular Agents / chemistry
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Antitubercular Agents / pharmacology*
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DNA Topoisomerases, Type I / metabolism*
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DNA, Bacterial / metabolism
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Humans
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Molecular Docking Simulation
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Mycobacterium smegmatis / drug effects
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Mycobacterium smegmatis / enzymology
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Mycobacterium smegmatis / growth & development
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Mycobacterium tuberculosis / drug effects*
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Mycobacterium tuberculosis / enzymology*
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Mycobacterium tuberculosis / growth & development
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Topoisomerase I Inhibitors / chemistry
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Topoisomerase I Inhibitors / pharmacology*
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Topoisomerase II Inhibitors / chemistry
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Topoisomerase II Inhibitors / pharmacology*
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Tuberculosis / drug therapy
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Tuberculosis / microbiology
Substances
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Antitubercular Agents
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DNA, Bacterial
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Topoisomerase I Inhibitors
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Topoisomerase II Inhibitors
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Amsacrine
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DNA Topoisomerases, Type I