This structurally differentiated chemotype provides a promising starting point for further optimization as antitubercular agent and led to analogs 21 and 24 with substantially improved antimycobacterial potency.
Abstract
Screening of the open-access CRESTdb small-molecule library identified the imidazothiazole carboxamide sCQG200 (1) as an initial hit, with activity against H37Rv and Erdman Mycobacterium tuberculosis strains in cholesterol-containing medium (MIC90= 6.88 µM and 4.48 µM, respectively) and against intracellular Mtb (EC50= 3.80 µM). sCQG200 retained activity against drug-resistant Mtb strains, including clinical MDR/XDR isolates. SAR optimization led to analogs 21 and 24 with substantially improved antimycobacterial potency. Mouse pharmacokinetic studies following oral and intravenous administration showed 62.1% and 29.5% oral bioavailability for 21 and 24, respectively. This structurally differentiated chemotype provides a promising starting point for further optimization as antitubercular agent.
Rv1625c/Cya has emerged as a promising target for the development of treatment-shortening therapies for tuberculosis. Screening of an Enamine compound library identified sBQQ004 as an initial hit, and rapid hit optimization led to compound 1, which was subsequently confirmed as an Rv1625c/Cya agonist. Structure–activit...
Han Xie, Paridhi Sukheja, Kirsten T. Tolentino et al.· bioRxiv· 0 citations
This study aims to identify potential inhibitors of the Ag85C enzyme from Mycobacterium tuberculosis through primary docking, pharmacophore modelling, and ADME/pharmacokinetics analysis, yielding three promising candidates.
Katewad Raghavendra Singh, Anuradha, C. Kumar· bioRxiv· 0 citations
Despite the availability of multiple treatment options, the emergence of drug-resistant Mycobacterium tuberculosis (Mtb) strains presents a significant health concern worldwide. This necessitates the development of novel antitubercular agents with distinct mechanisms of action. Diaminoquinazolines (DAQs) have demonstra...
Mukul Kore, N. Sundaramoorthy, Saqib Kidwai et al.· RSC Advances· 0 citations
A library of 52 indolo[2,3-b]quinoxaline derivatives was designed and synthesized using a pharmacophore-hybridization strategy and subjected to comprehensive biological and computational evaluation, highlighting indolo[2,3-b]quinoxaline as promising antitubercular scaffold for further development.
Sri Mounika Bellapukonda, Akanksha, Mainak Ghosh et al.· European journal of medicina...· 0 citations
In vitro findings identified compounds 6a, 6m, and 6n as potent leads, exhibiting significant antimicrobial activity with minimum inhibitory concentration values ranging from 15 to 500 µg/mL and antioxidant activity with DPPH IC50 values of 6.35 ± 0.51 μM, respectively.
Preetesh Kumar Panda, S. Paidesetty, Alaka Sahoo et al.· Future Medicinal Chemistry· 0 citations
Findings highlight the potential of benzisothiazole‐based hydrazide derivatives as promising scaffolds for the development of new antitubercular agents and suggest InhA as a potential molecular target.
V. Sharma, Arun Sharma, Ruchi Poria et al.· Chemical Biology and Drug De...· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
