1268243-10-2Relevant academic research and scientific papers
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
experimental part, 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.
