title: Synthesis, antitubercular activity, and SAR study of N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazides.
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.
authors.affiliation: Universidade Federal Fluminense, Departamento de Química Orgânica, Instituto de Química, Outeiro de São João Baptista, 24020-141 Niterói, RJ, Brazil.
authors.forename: Alessandro K
authors.initials: AK
authors.lastname: Jordão
authors.forename: Plínio C
authors.initials: PC
authors.lastname: Sathler
authors.forename: Vitor F
authors.initials: VF
authors.lastname: Ferreira
authors.forename: Vinícius R
authors.initials: VR
authors.lastname: Campos
authors.forename: Maria C B V
authors.initials: MC
authors.lastname: de Souza
authors.forename: Helena C
authors.initials: HC
authors.lastname: Castro
authors.forename: Andressa
authors.initials: A
authors.lastname: Lannes
authors.forename: André
authors.initials: A
authors.lastname: Lourenco
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Rodrigues
authors.forename: Murilo L
authors.initials: ML
authors.lastname: Bello
authors.forename: Maria C S
authors.initials: MC
authors.lastname: Lourenco
authors.forename: Guilherme S L
authors.initials: GS
authors.lastname: Carvalho
authors.forename: Maria C B
authors.initials: MC
authors.lastname: Almeida
authors.forename: Anna C
authors.initials: AC
authors.lastname: Cunha
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006834:Hydrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry*
chemical_list: D000995:Antitubercular Agents; D006834:Hydrazines; D014230:Triazoles; C019289:carbohydrazide