@article{10.37349/eds.2026.1008145,
abstract = {Aim: To design, synthesize, and test small molecules and fragment-based compounds with putative selective anti-mycobacterial activity. Methods: Standard chemosynthetic processes were used to synthesize 42 compounds. A cell-based phenotypic screen for inhibitors of mycobacterial growth was used to identify several fragments and small molecules as representatives of urea-, carbamothioate-, and α,β-unsaturated systems (Michael acceptors) chemotypes. Results: All 42 compounds exhibited selective toxicity for mycobacteria as demonstrated by their lack of activity against various Gram-positive and Gram-negative bacteria and acid-fast Corynebacterium glutamicum. A thiadiazole compound, similar to (3-((5-(methylthio)-1,3,4-thiadiazol-2-yl)thio)pyrazine-2-carbonitrile), which activates the human lecitin: cholesterol acyltransferase (LCAT), exhibits growth-inhibitory activity [0.6 μg/mL in bovine serum albumin (BSA)-free media] against drug-susceptible Mycobacterium tuberculosis (Mtb). From the urea class, a 1,2,4-triazole-containing urea demonstrated anti-Mtb activity (4.7 μg/mL in BSA-free media). Several carbamothioate-based fragments demonstrated activity against Mycobacterium marinum [with a best minimum inhibitory concentration (MIC) of 6.25 μg/mL in minimal BSA-free media]. Conclusions: This foundational study demonstrates the utility of these newly designed and synthesized low molecular-weight compounds and fragments as potential antimycobacterials.},
author = {Konaklieva, Monika I. and Arora, Kriti and Boshoff, Helena I. M. and Plotkin, Balbina J.},
doi = {10.37349/eds.2026.1008145},
journal = {Exploration of Drug Science},
elocation-id = {1008145},
title = {Small molecule and fragment-based phenotypic screening for novel building blocks with antimycobacterial activity},
url = {https://www.explorationpub.com/Journals/eds/Article/1008145},
volume = {4},
year = {2026}
}