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General Content - Research Article

Tailored-pharmacophore model to enhance virtual screening and drug discovery: a case study on the identification of potential inhibitors against drug-resistant Mycobacterium tuberculosis (3R)-hydroxyacyl-ACP dehydratases

    Kgothatso E Machaba

    Molecular Modelling & Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4001, South Africa

    ,
    Ndumiso N Mhlongo

    School of Laboratory Medicine & Medical Sciences, University of KwaZulu-Natal, Durban 4001, South Africa

    ,
    Yussif M Dokurugu

    College of Pharmacy & Pharmaceutical Sciences, Florida Agricultural & Mechanical University, FAMU, Tallahassee, FL 32307, USA

    &
    Mahmoud ES Soliman

    *Author for correspondence:

    E-mail Address: soliman@ukzn.ac.za

    Molecular Modelling & Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4001, South Africa

    College of Pharmacy & Pharmaceutical Sciences, Florida Agricultural & Mechanical University, FAMU, Tallahassee, FL 32307, USA

    Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt

    Published Online:https://doi.org/10.4155/fmc-2017-0020

    Aim: Virtual screening (VS) is powerful tool in discovering molecular inhibitors that are most likely to bind to drug targets of interest. Herein, we introduce a novel VS approach, so-called ‘tailored-pharmacophore’, in order to explore inhibitors that overcome drug resistance. Methodology & results: The emergence and spread of drug resistance strains of tuberculosis is one of the most critical issues in healthcare. A tailored-pharmacophore approach was found promising to identify in silico predicted hit with better binding affinities in case of the resistance mutations in MtbHadAB as compared with thiacetazone, a prodrug used in the clinical treatment of tuberculosis. Conclusion: This approach can potentially be enforced for the discovery and design of drugs against a wide range of resistance targets.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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