Synthesis, antitubercular activity, and SAR study of N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazides
| Autor: | Carlos Rangel Rodrigues, Vinícius R. Campos, Andressa C. Lannes, Maria C.S. Lourenço, Maria C.B. Almeida, Helena Carla Castro, Plínio Cunha Sathler, Maria Cecília B. V. de Souza, Anna C. Cunha, Guilherme S. L. Carvalho, Vitor F. Ferreira, Alessandro K. Jordão, André Luiz Lourenço, Murilo Lamim Bello |
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| Jazyk: | angličtina |
| Předmět: |
Models
Molecular 1 2 3-Triazole Stereochemistry Clinical Biochemistry Antitubercular Agents Pharmaceutical Science Infrared spectroscopy Microbial Sensitivity Tests Biochemistry chemistry.chemical_compound Structure-Activity Relationship Drug Discovery Molecule Molecular Biology Medicine(all) biology Dose-Response Relationship Drug Molecular Structure Chemistry Small volume 1 2 3-Triazole derivatives Organic Chemistry Stereoisomerism Mycobacterium tuberculosis Triazoles biology.organism_classification NMR spectra database Diazocompounds Hydrazines Lipophilicity Mycobacterium tuberculosis H37Rv Molecular Medicine Carbohydrazides Mycobacterium |
| Zdroj: | Bioorganic & Medicinal Chemistry. (18):5605-5611 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2011.07.035 |
| Popis: | 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-1 H -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. |
| Databáze: | OpenAIRE |
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