Abstract
In the present study, we identified carvacrol, a major phenolic component of oregano oil as a novel small molecule inhibitor of Mycobacterium tuberculosis (MTB) chorismate mutase (CM) enzyme with IC50 of 1.06 ± 0.4 µM. Virtual screening of the BITS-Pilani in-house database using the crystal structure of the MTB CM bound transition state intermediate (PDB: 2FP2) as framework identified carvacrol as a potential lead. Further various carvacrol derivatives were evaluated in vitro for their ability to inhibit MTB CM enzyme, whole cell MTB and cytotoxicity as steps toward the derivation of structure-activity relationships (SAR) and lead optimization.
Keywords:
Carvacrol; Mycobacterium tuberculosis; chorismate mutase.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Bacterial Agents / chemical synthesis
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Anti-Bacterial Agents / chemistry*
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Anti-Bacterial Agents / pharmacology*
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Chorismate Mutase / antagonists & inhibitors*
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Chorismate Mutase / metabolism
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Cymenes
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Dose-Response Relationship, Drug
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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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Microbial Sensitivity Tests
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Models, Molecular
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Molecular Structure
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Monoterpenes / chemical synthesis
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Monoterpenes / chemistry
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Monoterpenes / pharmacology*
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Mycobacterium tuberculosis / cytology
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Mycobacterium tuberculosis / drug effects
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Mycobacterium tuberculosis / enzymology*
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Structure-Activity Relationship
Substances
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Anti-Bacterial Agents
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Cymenes
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Enzyme Inhibitors
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Monoterpenes
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carvacrol
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Chorismate Mutase