349120-93-0Relevant articles and documents
2-(Quinolin-4-yloxy)acetamides Are Active against Drug-Susceptible and Drug-Resistant Mycobacterium tuberculosis Strains
Pissinate, Kenia,Villela, Anne Drumond,Rodrigues, Valnês,Giacobbo, Bruno Couto,Grams, Estêv?o Silveira,Abbadi, Bruno Lopes,Trindade, Rogério Valim,Roesler Nery, Laura,Bonan, Carla Denise,Back, Davi Fernando,Campos, Maria Martha,Basso, Luiz Augusto,Santos, Diógenes Santiago,Machado, Pablo
, p. 235 - 239 (2016)
2-(Quinolin-4-yloxy)acetamides have been described as potent in vitro inhibitors of Mycobacterium tuberculosis growth. Herein, additional chemical modifications of lead compounds were carried out, yielding highly potent antitubercular agents with minimum inhibitory concentration (MIC) values as low as 0.05 μM. Further, the synthesized compounds were active against drug-resistant strains and were devoid of apparent toxicity to Vero and HaCat cells (IC50s ≥ 20 μM). In addition, the 2-(quinolin-4-yloxy)acetamides showed intracellular activity against the bacilli in infected macrophages with action similar to rifampin, low risk of drug-drug interactions, and no sign of cardiac toxicity in zebrafish (Danio rerio) at 1 and 5 μM. Therefore, these data indicate that this class of compounds may furnish candidates for future development to, hopefully, provide drug alternatives for tuberculosis treatment.
Synthesis and evaluation of thiazolyl-1H-benzo[d]imidazole inhibitors of Mycobacterium tuberculosis inosine monophosphate dehydrogenase
Pissinate, Kenia,Rostirolla, Diana Carolina,Pinheiro, Laura Miranda,Suryadevara, Priyanka,Yogeeswari, Perumal,Sriram, Dharmarajan,Basso, Luiz Augusto,Machado, Pablo,Santos, Diógenes Santiago
, p. 1357 - 1366 (2015/07/15)
Using an orthologue-based design approach, we synthesized and assayed a series of thiazolyl-1H-benzo[d]imidazole derivatives as inhibitors of Mycobacterium tuberculosis inosine 5′-monophosphate dehydrogenase (MtIMPDH). From these experiments, a benzo[d] imidazole compound was described to inhibit the enzyme in the low micromolar range (KiIMP = 0.55 ± 0.02 μM), which places this compound among the most potent in vitro MtIMPDH inhibitors developed to date. In addition, steady-state kinetic measurements and docking simulations were employed to determine its inhibition and interaction modes. The results described herein may be useful for the design and development of novel alternative therapeutics for tuberculosis that target MtIMPDH, a predicted to be essential (for optimal in vitro bacillus growth), druggable and assayable molecular target.
