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.
| Autor: | Machaba KE; Molecular Modelling & Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4001, South Africa., Mhlongo NN; School of Laboratory Medicine & Medical Sciences, University of KwaZulu-Natal, Durban 4001, South Africa., Dokurugu YM; College of Pharmacy & Pharmaceutical Sciences, Florida Agricultural & Mechanical University, FAMU, Tallahassee, FL 32307, USA., Soliman ME; 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. |
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| Jazyk: | angličtina |
| Zdroj: | Future medicinal chemistry [Future Med Chem] 2017 Jun; Vol. 9 (10), pp. 1055-1071. Date of Electronic Publication: 2017 Jun 20. |
| DOI: | 10.4155/fmc-2017-0020 |
| Abstrakt: | 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. |
| Databáze: | MEDLINE |
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