PUBLICATION
2-(Quinolin-4-yloxy)acetamides Are Active against Drug-Susceptible and Drug-Resistant Mycobacterium tuberculosis Strains
- Authors
- Pissinate, K., Villela, A.D., Rodrigues-Junior, V., Giacobbo, B.C., Grams, E.S., Abbadi, B.L., Trindade, R.V., Roesler Nery, L., Bonan, C.D., Back, D.F., Campos, M.M., Basso, L.A., Santos, D.S., Machado, P.
- ID
- ZDB-PUB-160318-3
- Date
- 2016
- Source
- ACS Medicinal Chemistry Letters 7: 235-9 (Journal)
- Registered Authors
- Bonan, Carla Denise
- Keywords
- SAR, Tuberculosis, drug-resistant research, quinoline-based compounds
- MeSH Terms
- none
- PubMed
- 26985307 Full text @ ACS Med. Chem. Lett.
Citation
Pissinate, K., Villela, A.D., Rodrigues-Junior, V., Giacobbo, B.C., Grams, E.S., Abbadi, B.L., Trindade, R.V., Roesler Nery, L., Bonan, C.D., Back, D.F., Campos, M.M., Basso, L.A., Santos, D.S., Machado, P. (2016) 2-(Quinolin-4-yloxy)acetamides Are Active against Drug-Susceptible and Drug-Resistant Mycobacterium tuberculosis Strains. ACS Medicinal Chemistry Letters. 7:235-9.
Abstract
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.
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