1268243-13-5Relevant academic research and scientific papers
Triazolophthalazines: Easily Accessible Compounds with Potent Antitubercular Activity
Veau, Damien,Krykun, Serhii,Mori, Giorgia,Orena, Beatrice S.,Pasca, Maria R.,Frongia, Céline,Lobjois, Valérie,Chassaing, Stefan,Lherbet, Christian,Baltas, Michel
, p. 1078 - 1089 (2016/06/01)
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 -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. Old trick, new drugs: A series of triazolophthalazines were synthesized and evaluated as potential antitubercular agents. A number of these easy-to-prepare compounds proved to be highly potent inhibitors of Mycobacterium tuberculosis (M.tb) and exhibited similar potency against multidrug-resistant M.tb strains.
Design, synthesis, and biological evaluation of new cinnamic derivatives as antituberculosis agents
De, Prithwiraj,Koumba Yoya, Georges,Constant, Patricia,Bedos-Belval, Florence,Duran, Hubert,Saffon, Nathalie,Daffé, Mamadou,Baltas, Michel
, p. 1449 - 1461 (2011/05/05)
Tuberculosis, HIV coinfection with TB, emergence of multidrug-resistant TB, and extensively drug-resistant TB are the major causes of death from infectious diseases worldwide. Because no new drug has been introduced in the last several decades, new classes of molecules as anti-TB drugs are urgently needed. Herein, we report the synthesis and structure-activity relationships of a series of thioester, amide, hydrazide, and triazolophthalazine derivatives of 4-alkoxy cinnamic acid. Many compounds exhibited submicromolar minimum inhibitory concentrations against Mycobacterium tuberculosis strain (H37Rv). Interestingly, compound 13e, a 4-isopentenyloxycinnamyl triazolophthalazine derivative, was found to be 100-1800 times more active than isoniazid (INH) when tested for its ability to inhibit the growth of INH-resistant M. tuberculosis strains. The results also revealed that 13e does not interfere with mycolic acid biosynthesis, thereby pointing to a different mode of action and representing an attractive lead compound for the development of new anti-TB agents.
