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.authorShahbaaz, Mohden_ZA
dc.contributor.authorCloete, Rubenen_ZA
dc.contributor.authorGrobbelaar, Melanieen_ZA
dc.contributor.authorSampson, Samanthaen_ZA
dc.contributor.authorChristoffels, Alanen_ZA
dc.date.accessioned2021-11-25T09:07:38Z
dc.date.available2021-11-25T09:07:38Z
dc.date.issued2019
dc.descriptionCITATION: Shahbaaz, M., et al. 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.2019.05.108.
dc.descriptionThe original publication is available at https://www.sciencedirect.com/
dc.description.abstractENGLISH ABSTRACT: The shortcomings of conventional tuberculosis treatments resulting from the development of drug resistance in Mycobacterium tuberculosis 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_ZA
dc.description.urihttps://www.sciencedirect.com/science/article/pii/S0141813019310955
dc.description.versionPublisher's version
dc.format.extent9 pagesen_ZA
dc.identifier.citationShahbaaz, M., et al. 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.2019.05.108
dc.identifier.issn0141-8130 (print)
dc.identifier.otherdoi:10.1016/j.ijbiomac.2019.05.108
dc.identifier.urihttp://hdl.handle.net/10019.1/123499
dc.language.isoen_ZAen_ZA
dc.publisherElsevieren_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectMycobacterium tuberculosisen_ZA
dc.subjectATP synthaseen_ZA
dc.subjectPharmacophore modelingen_ZA
dc.subjectMolecular dockingen_ZA
dc.subjectMolecular dynamic simulationsen_ZA
dc.titleStructure based identification of novel inhibitors against ATP synthase of Mycobacterium tuberculosis : a combined in silico and in vitro studyen_ZA
dc.typeArticleen_ZA
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