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

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) - FCFRP

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