1426068-32-7Relevant articles and documents
Structure-activity relationships of antitubercular salicylanilides consistent with disruption of the proton gradient via proton shuttling
Lee, Ill-Young,Gruber, Todd D.,Samuels, Amanda,Yun, Minhan,Nam, Bora,Kang, Minseo,Crowley, Kathryn,Winterroth, Benjamin,Boshoff, Helena I.,Barry III, Clifton E.
, p. 114 - 126 (2013/02/22)
A series of salicylanilides was synthesized based on a high-throughput screening hit against Mycobacterium tuberculosis. A free phenolic hydroxyl on the salicylic acid moeity is required for activity, and the structure-activity relationship of the aniline ring is largely driven by the presence of electron withdrawing groups. We synthesized 94 analogs exploring substitutions of both rings and the linker region in this series and we have identified multiple compounds with low micromolar potency. Unfortunately, cytotoxicity in a murine macrophage cell line trends with antimicrobial activity, suggesting a similar mechanism of action. We propose that salicylanilides function as proton shuttles that kill cells by destroying the cellular proton gradient, limiting their utility as potential therapeutics.
Development of 5-nitrothiazole derivatives: Identification of leads against both replicative and latent Mycobacterium tuberculosis
Jeankumar, Variam Ullas,Chandran, Manoj,Samala, Ganesh,Alvala, Mallika,Koushik, Pulla Venkat,Yogeeswari, Perumal,Salina, Elena G.,Sriram, Dharmarajan
, p. 7414 - 7417 (2013/02/22)
Twenty eight 5-nitrothiazole derivatives were synthesized and evaluated for in vitro activities against Mycobacterium tuberculosis (MTB), cytotoxicity against HEK 293T. Among the compounds, 5-nitro-N-(5-nitrothiazol-2-yl)furan-2- carboxamide (20) was found to be the most active compound in vitro with MICs of 5.48 μM against log-phase culture of MTB and also non-toxic up to 100 μM.