A new bianthron glycoside as inhibitor of Trypanosoma cruzi glyceraldehyde 3-phosphate dehydrogenase activity

Abstract

A phytochemical investigation of the ethanolic extract of stalks of Senna martiana Benth. (Leguminoseae), native specie of northeast Brazil, resulted in the isolation and spectroscopic characterization of a new bianthrone glycoside, martianine 1 (10,10'-il-chrysophanol-10-oxi10,10'-bi-glucosyl). Its identification was established by HRMS, IR and 2D NMR experiments. The evaluation of martianine trypanocidal activity was carried out against gliceraldehyde 3-phosphate dehydrogenase enzyme from Trypanosoma cruzi. Its inhibitory constant (Ki) is in the low micromolar concentration and it was determined by isothermal titration calorimetry to be 27.3 ± 2.47 µmol L-1. The non-competitive mechanism is asserted to be putative of the mode of action martianine displays against T. cruzi GAPDH. Results show that martianine has a great potential to become new lead molecule by inhibiting this key enzyme and for the development of new drugs against Chagas disease.A investigação fitoquímica do extrato etanólico do caule de Senna martiana Benth. (Leguminoseae), espécie nativa do nordeste do Brasil, permitiu o isolamento e caracterização espectroscópica de uma biantrona inédita denominada martianina (1), 10,10'-H-bicrisofanol10-ox-10,10'-biglucosil. Sua identificação estrutural inequívoca foi estabelecida por HRMS, IV e RMN de ¹H e 13C uni e bi-dimensional. A atividade tripanocida de martianina foi avaliada por seu comportamento frente à enzima GAPDH Tc através da obtenção de sua constante de inibição (Ki) determinada por titulação calorimétrica isotérmica (27,3 ± 2,47 µmol L-1). Estes resultados sugerem que esta classe de molécula tem potencial no desenvolvimento de novos fármacos a serem utilizados contra a doença de Chagas.Universidade de São Paulo (USP) - FCFRPFUNCAPFAPES