pbtz169 and nitromide

Non-tuberculous mycobacteria (NTM) infections are increasingly being reported worldwide. They are a major concern for healthcare professionals for multiple reasons, ranging from the intrinsic resistance of NTM to most conventionally utilized antimicrobials to inharmonious diagnostic criteria utilized for evaluation of NTM-infected patients, leading to high morbidity. In this review, we highlight the paucity of drugs having potent anti-NTM activity amongst the new antimicrobials currently under various stages of development for anti-tubercular activity and issue a call for the establishment of a concerted dedicated drug discovery pipeline targeting NTM.

Topics: Adamantane; Aminopyridines; Anti-Bacterial Agents; Azepines; Benzamides; Clinical Trials as Topic; Diarylquinolines; Drug Discovery; Ethylenediamines; Fluoroquinolones; Humans; Minocycline; Mycobacterium Infections, Nontuberculous; Nitroimidazoles; Nontuberculous Mycobacteria; Oxazoles; Piperazines; Spiro Compounds; Thiazines; Tigecycline; Uridine

We report herein the design, synthesis and antimycobacterial activity of 3,5-dinitrobenzamide derivatives containing fused ring moieties. Results reveal that many of the target compounds have considerable in vitro antitubercular activity. Especially, N-((2-(4-fluorophenyl)/N-((2-(3-fluorobenzyl)-1,2,3,4-tetrahydroisoquilin-6-yl)methyl)-3,5-dinitrobenzamides 18a and 20e exhibit potent MIC values of 0.056-0.078 μg/mL against both drug-sensitive Mycobacterium tuberculosis (MTB) H37Rv strain and two clinically isolated multidrug-resistant MTB (MDR-MTB) strains, opening a new direction for further SAR studies.

Topics: Anti-Bacterial Agents; Benzamides; Dose-Response Relationship, Drug; Drug Design; Microbial Sensitivity Tests; Molecular Structure; Mycobacterium tuberculosis; Structure-Activity Relationship