1. Synthesis, antitubercular activity, and SAR study of N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazides.
- Author
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Jordão AK, Sathler PC, Ferreira VF, Campos VR, de Souza MC, Castro HC, Lannes A, Lourenco A, Rodrigues CR, Bello ML, Lourenco MC, Carvalho GS, Almeida MC, and Cunha AC
- Subjects
- Antitubercular Agents chemistry, Dose-Response Relationship, Drug, Hydrazines chemical synthesis, Hydrazines chemistry, Microbial Sensitivity Tests, Models, Molecular, Molecular Structure, Stereoisomerism, Structure-Activity Relationship, Antitubercular Agents chemical synthesis, Antitubercular Agents pharmacology, Hydrazines pharmacology, Mycobacterium tuberculosis drug effects, Triazoles chemistry
- Abstract
Tuberculosis treatment remains a challenge that requires new antitubercular agents due to the emergence of multidrug-resistant Mycobacterium strains. This paper describes the synthesis, the antitubercular activity and the theoretical analysis of N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazides (8a-b, 8e-f, 8i-j and 8n-o) and new analogues (8c-d, 8g-h, 8l-m and 8p-q). These derivatives were synthesized in good yields and some of them showed a promising antitubercular profile. Interestingly the N-acylhydrazone (NAH) 8n was the most potent against the Mycobacterium tuberculosis H37Rv strain (MIC=2.5 μg/mL) similar to or better than the current drugs on the market. The theoretical structure-activity relationship study suggested that the presence of the furyl ring and the electronegative group (NO(2)) as well as low lipophilicity and small volume group at R position are important structural features for the antitubercular profile of these molecules. NMR spectra, IR spectra and elemental analyses of these substances are reported., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2011
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