Juan Gayosso-De-Lucio, Martin Torres-Valencia, Arturo Rojo-Domínguez, Hugo Nájera-Peña, Beatriz Aguirre-López, José Salas-Pacheco, Claudia Avitia-Domínguez, Alfredo Téllez-Valencia., Selective inactivation of triosephosphate isomerase from Trypanosoma cruzi by brevifolin carboxylate derivativesisolated from Geranium bellum Rose, Bioorganic & Medicinal Chemistry Letters, Año: 2009 Volume 19, Issue 20, 15 Pages 5936-5939 DOI:10.1016/j.bmcl.2009.08.055 ISSN: 0960-894X
In the search of molecules that can serve as leads in the design of a new drug for the treatment of Chagas'disease, we found that some brevifolin carboxylate derivatives isolated from Geranium bellum Rose, inactivatetriosephosphate isomerase from Trypanosoma cruzi (TcTIM) in a species-specific manner. After spectroscopiccharacterization, these compounds were identified as methylbrevifolin carboxylate (1), ethylbrevifolin carboxylate (2),butylbrevifolin carboxylate (3) and the methylated derivate methyl tri-O-methylbrevifolin carboxylate (4). Theconcentrations required to inactivate fifty percent the activity of TcTIM were 6.5, 8 and 14 mu M of 1, 2 and 3,respectively, while compound 4 had no inhibitory effect. Molecular docking simulations of 1 on the structure of TcTIMshowed that residues of both monomers interact with the compound. These compounds are very selective with respect tothe parasite enzyme, since they showed no effect on the activity of human TIM at concentrations as high as 1 mM. Inconclusion, the brevifolin carboxylate derivatives described here are excellent leads in the search of a new chemotherapyfor the treatment of this disease.