Structure based identification of novel inhibitors against ATP synthase of Mycobacterium tuberculosis: A combined in silico and in vitro study

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dc.contributor.authorCloete, Ruben
dc.contributor.authorGrobbelaar, Melanie
dc.contributor.authorSampson, Samantha
dc.contributor.authorChristoffels, Alan
dc.date.accessioned2020-02-12T12:44:25Z
dc.date.available2020-02-12T12:44:25Z
dc.date.issued2019
dc.description.abstractThe shortcomings of conventional tuberculosis treatments resulting from the development of drug resistance in Mycobacteriumtuberculosis drive a need for the formulation of novel therapeutic agents. The diarylquinoline class of drugs such as bedaquiline was recently approved for the treatment of multidrug-resistant strains of tuberculosis, primarily targeting c and ε subunits of the ATP synthases. Yet resistance to bedaquiline has already been reported. Therefore, Rv1311 was used as the target for the identification of possible inhibitors against the M. tuberculosis. The structure of Rv1311 was predicted and common feature pharmacophore models were generated which facilitated the identification of potential inhibitors in the ZINC database. The activities of the selected molecules were compared with known inhibitors of the ATP synthase using quantitative structure– activity relationship. The ZINC classified inhibitors showed comparable predicted activities with that of known inhibitors. Furthermore, the inhibitory behavior of the studied drug molecules was experimentally determined using in vitro techniques and showed the minimum inhibitory concentration as low as 25 μM. The resulted outcomes provide a deeper insight into the structural basis of Rv1311 inhibitions and can facilitate the process of drug design against tuberculosis.en_US
dc.identifier.citationShahbaaz, M., Cloete, R., Grobbelaar, M., Sampson, S., & Christoffels, A. (2019). Structure based identification of novel inhibitors against ATP synthase of mycobacterium tuberculosis: A combined in silico and in vitro study. International Journal of Biological Macromolecules, 135, 582-590. doi:10.1016/j.ijbiomac.2019.05.108en_US
dc.identifier.issn01418130
dc.identifier.urihttp://hdl.handle.net/10566/5175
dc.language.isoenen_US
dc.publisherInternational Journal of Biological Macromoleculesen_US
dc.subjectMycobacterium tuberculosisen_US
dc.subjectATP synthaseen_US
dc.subjectPharmacophore modelingen_US
dc.subjectMolecular dockingen_US
dc.subjectMolecular dynamic simulationsen_US
dc.titleStructure based identification of novel inhibitors against ATP synthase of Mycobacterium tuberculosis: A combined in silico and in vitro studyen_US
dc.typeArticleen_US

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