Synthesis and evaluation of α-ketotriazoles and α,β-diketotriazoles as inhibitors of Mycobacterium tuberculosis

• DOI: 10.1016/j.ejmech.2013.06.042
• Publication Date: 2013-07-08T12:18:31Z
• Authors: Christophe Menendez; Frédéric Rodriguez; Ana Luisa de Jesu...; Francesca Zara; Céline Frongia; Valérie Lobjois; Nathalie Saffon; Maria Rosalia Pasca; Christian Lherbet; Michel Baltas
• Keywords: 0303 health sciences; Dose-Response Relationship, Drug; Molecular Structure; Mycobacterium tuberculosi; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Ketones; Triazoles; HCT116 Cells; Anti-Bacterial Agents; 3. Good health; Structure-Activity Relationship; 03 medical and health sciences; Humans; Antitubercular drug

Two series of α-ketotriazole and α,β-diketotriazole derivatives were synthesized and evaluated for antitubercular and cytotoxic activities. Among them, two α,β-diketotriazole compounds, 6b and 9b, exhibited good activities (minimum inhibitory concentration = 7.6 μM and 6.9 μM, respectively) on Mycobacterium tuberculosis and multi-drug resistant M. tuberculosis strains and presented no cytotoxicity (IC₅₀ > 50 μM) on colorectal cancer HCT116 and normal fibroblast GM637H cell lines. These two compounds represent promising leads for further optimization.