Abstract
We report here the discovery, synthesis and screening results of a series of 3-(9H-fluoren-9-yl)pyrrolidine-2,5-dione derivatives as a novel class of potent inhibitors of Mycobacterium tuberculosis H37Rv strain as well as the enoyl acyl carrier protein reductase (ENR) InhA. Among them, several compounds displayed good activities against InhA which is one of the key enzymes involved in the type II fatty acid biosynthesis pathway of the mycobacteria cell wall. Furthermore, some exhibited promising activities against M. tuberculosis and multi-drug resistant M. tuberculosis strains.
Keywords:
3-(9H-Fluoren-9-yl)pyrrolidine-2,5-dione; InhA; Inhibition; Mycobacterium tuberculosis; Succinimide.
Copyright © 2013 Elsevier Masson SAS. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antitubercular Agents / chemical synthesis
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Antitubercular Agents / chemistry
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Antitubercular Agents / pharmacology*
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Bacterial Proteins / antagonists & inhibitors*
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Bacterial Proteins / metabolism
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Dose-Response Relationship, Drug
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Drug Design*
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Kinetics
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Microbial Sensitivity Tests
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Models, Molecular
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Molecular Structure
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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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Oxidoreductases / antagonists & inhibitors*
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Oxidoreductases / metabolism
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Pyrrolidinones / chemical synthesis
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Pyrrolidinones / chemistry
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Pyrrolidinones / pharmacology*
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Structure-Activity Relationship
Substances
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3-(9H-fluoren-9-yl)pyrrolidine-2,5-dione
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Antitubercular Agents
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Bacterial Proteins
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Enzyme Inhibitors
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Pyrrolidinones
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Oxidoreductases
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InhA protein, Mycobacterium