Preliminary Structure-Activity Relationships and Biological Evaluation of Novel Antitubercular Indolecarboxamide Derivatives Against Drug-Susceptible and Drug-Resistant Mycobacterium tuberculosis Strains
MetadataShow full item record
Tuberculosis (TB) remains one of the leading causes of mortality and morbidity worldwide, with approximately one-third of the world’s population infected with latent TB. This is further aggravated by HIV coinfection and the emergence of multidrug- and extensively drug-resistant (MDR and XDR, respectively) TB; hence the quest for highly effective antitubercular drugs with novel modes of action is imperative. We report herein the discovery of an indole-2-carboxamide analogue, 3, as a highly potent antitubercular agent, and the subsequent chemical modifications aimed at establishing a preliminary body of structure–activity relationships (SARs). These efforts led to the identification of three molecules (12–14) possessing an exceptional activity in the low nanomolar range against actively replicating Mycobacterium tuberculosis, with minimum inhibitory concentration (MIC) values lower than those of the most prominent antitubercular agents currently in use. These compounds were also devoid of apparent toxicity to Vero cells. Importantly, compound 12 was found to be active against the tested XDR-TB strains and orally active in the serum inhibition titration assay.
Showing items related by title, author, creator and subject.
Identification of Novel Coumestan Derivatives as Polyketide Synthase 13 Inhibitors against Mycobacterium tuberculosisZhang, W.; Lun, S.; Wang, S.; Jiang, X.; Yang, F.; Tang, J.; Manson, A.; Earl, A.; Gunosewoyo, Hendra; Bishai, W.; Yu, L. (2018)© 2018 American Chemical Society. Inhibition of the mycolic acid pathway has proven a viable strategy in antitubercular drug discovery. The AccA3/AccD4/FadD32/Pks13 complex of Mycobacterium tuberculosis constitutes an ...
Mortality from adverse drug reaction-related hospitalizations in south-west Ethiopia: A cross-sectional studyAngamo, M.; Chalmers, Leanne; Curtain, C.; Yilma, D.; Bereznicki, L. (2018)© 2018 John Wiley & Sons Ltd. What is known and objective: Adverse drug reactions (ADRs) are an important cause of mortality during medical care. To our knowledge, no Ethiopian studies have reported on mortality due to ...
Predictors of adverse drug reaction-related hospitalisation in Southwest Ethiopia: A prospective cross-sectional studyAngamo, M.; Curtain, C.; Stafford, Leanne; Yilma, D.; Bereznicki, L. (2017)© 2017 Angamo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the ...