Design and Synthesis of Novel Triazoloquinazolin-5(3H)-one Analogues as Promising Antitubercular Agents

• Published in: Russian journal of general chemistry Vol. 94; no. 8; pp. 2152 - 2166
• Main Authors: Appani, Ramgopal, Sumakanth, M.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01.08.2024; Springer Nature B.V
• Subjects: Chemistry; Chemistry and Materials Science; Chemistry/Food Science; In vivo methods and tests; NMR; Nuclear magnetic resonance; Synthesis; antitubercular activity; triazoloquinazolinone; H37Ra; H37Rv; female BALB/c mice
• ISSN: 1070-3632; 1608-3350
• DOI: 10.1134/S1070363224080255

A series of novel 3,4,7- or 3,4,8-trisubstituted-3a,4-dihydro[1,2,3]triazolo[1,5- a ] quinazolin-5(3 H )-one analogues was synthesized and characterized by using HRMS, 1 H NMR and 13 C NMR spectral data. All the compounds were tested for their in vitro antitubercular activity by using the Microplate Alamar Blue Assay technique, the minimum inhibitory concentration values of the most effective inhibitors were determined for Mycobacterium tuberculosis H37Rv and H37Ra strains by using rifampicin, isoniazid and ethambutol as reference standards. Among all synthesized compounds 7-chloro-3-(3-chloropyridin-4-yl)-4-methyl[1,2,3]triazolo[1,5- a ]quinazolin-5(4 H )-one, 7-bromo-8-chloro-4-(4-fluorophenyl)-3-(3-methylpyridin-4-yl)[1,2,3]triazolo[1,5- a ]quinazolin-5(4 H )-one and 7-bromo-4-(4-methoxyphenyl)-3-(3-methylpyridin-4-yl)-[1,2,3]triazolo[1,5- a ]quinazolin-5(4 H )-one exhibit excellent in vitro antitubercular activity when compared to the reference standards. Further 7-bromo-8-chloro-4-(4-fluorophenyl)-3-(3-methylpyridin-4-yl)[1,2,3]triazolo[1,5- a ]quinazolin-5(4 H )-one was evaluated for in vivo antitubercular activity after post treatment in female BALB/c mice by determination of log10 colony formation unit in lungs and spleen. Therefore, this compound could serve as the lead molecule for further development as antitubercular agent.