Triazolophthalazines: Easily Accessible Compounds with Potent Antitubercular Activity |
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Authors: | Dr Damien Veau Serhii Krykun Dr Giorgia Mori Dr Beatrice S Orena Dr Maria R Pasca Céline Frongia Dr Valérie Lobjois Dr Stefan Chassaing Dr Christian Lherbet Dr Michel Baltas |
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Affiliation: | 1. Laboratoire de Synthèse et Physicochimie de Molécules d'Intérêt Biologique (SPCMIB), CNRS-UMR5068, Université Paul Sabatier-Toulouse?III, Toulouse Cedex?9, France;2. ITAV, Université de Toulouse, CNRS, UPS, Toulouse Cedex?1, France;3. Dipartimento di Biologica e Biotecnologie 'Lazzaro Spallanzani', Pavia, Italy |
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Abstract: | Tuberculosis (TB) remains one of the major causes of death worldwide, in particular because of the emergence of multidrug‐resistant TB. Herein we explored the potential of an alternative class of molecules as anti‐TB agents. Thus, a series of novel 3‐substituted triazolophthalazines was quickly and easily prepared from commercial hydralazine hydrochloride as starting material and were further evaluated for their antimycobacterial activities and cytotoxicities. Four of the synthesized compounds were found to effectively inhibit the Mycobacterium tuberculosis (M.tb) H37Rv strain with minimum inhibitory concentration (MIC) values <10 μg mL?1, whereas no compounds displayed cytotoxicity against HCT116 human cell lines (IC50>100 μm ). More remarkably, the most potent compounds proved to be active to a similar extent against various multidrug‐resistant M.tb strains, thus uncovering a mode of action distinct from that of standard antitubercular agents. Overall, their ease of preparation, combined with their attractive antimycobacterial activities, make such triazolophthalazine‐based derivatives promising leads for further development. |
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Keywords: | antimycobacterial activity cytotoxicity organic synthesis triazolophthalazines tuberculosis |
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