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dc.contributor.authorAlsayed, Shahinda SR
dc.contributor.authorLun, Shichun
dc.contributor.authorLuna, Giuseppe
dc.contributor.authorBeh, Chau Chun
dc.contributor.authorPayne, Alan D
dc.contributor.authorFoster, Neil R
dc.contributor.authorBishai, William R
dc.contributor.authorGunosewoyo, Hendra
dc.identifier.citationAlsayed, S.S.R. and Lun, S. and Luna, G. and Beh, C.C. and Payne, A.D. and Foster, N.R. and Bishai, W.R. et al. 2020. Design, synthesis, and biological evaluation of novel arylcarboxamide derivatives as anti-tubercular agents. RSC Advances. 10: pp. 7523-7540.

Our group has previously reported several indolecarboxamides exhibiting potent antitubercular activity. Herein, we rationally designed several arylcarboxamides based on our previously reported homology model and the recently published crystal structure of the mycobacterial membrane protein large 3 (MmpL3). Many analogues showed considerable anti-TB activity against drug-sensitive (DS) Mycobacterium tuberculosis (M. tb) strain. Naphthamide derivatives 13c and 13d were the most active compounds in our study (MIC: 6.55, 7.11 μM, respectively), showing comparable potency to the first line anti-tuberculosis (anti-TB) drug ethambutol (MIC: 4.89 μM). In addition to the naphthamide derivatives, we also identified the quinolone-2-carboxamides and 4-arylthiazole-2-carboxamides as potential MmpL3 inhibitors in which compounds 8i and 18b had MIC values of 9.97 and 9.82 μM, respectively. All four compounds retained their high activity against multidrug-resistant (MDR) and extensively drug-resistant (XDR) M. tb strains. It is worth noting that the two most active compounds 13c and 13d also exhibited the highest selective activity towards DS, MDR and XDR M. tb strains over mammalian cells [IC50 (Vero cells) ≥ 227 μM], indicating their potential lack of cytotoxicity. The four compounds were docked into the MmpL3 active site and were studied for their drug-likeness using Lipinski's rule of five.

dc.titleDesign, synthesis, and biological evaluation of novel arylcarboxamide derivatives as anti-tubercular agents
dc.typeJournal Article
dcterms.source.titleRSC Advances
curtin.accessStatusOpen access
curtin.contributor.orcidBeh, Jane [0000-0002-5563-8795]
curtin.contributor.scopusauthoridBeh, Jane [55033508000]

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