Strategies for the isolation and identification of trypanocidal compounds from the Rutales

Vieira, Paulo C.; Mafezoli, Jair; Pupo, Mônica T.; Fernandes, João B.; da Silva, M. Fátima das G. F.; de Albuquerque, Sérgio; Oliva, Glaucius; Pavão, Fernando

doi:10.1351/pac200173030617

Pure Appl. Chem., 2001, Vol. 73, No. 3, pp. 617-622

http://dx.doi.org/10.1351/pac200173030617

Strategies for the isolation and identification of trypanocidal compounds from the Rutales

Paulo C. Vieira¹*, Jair Mafezoli¹, Mônica T. Pupo², João B. Fernandes¹, M. Fátima das G. F. da Silva¹, Sérgio de Albuquerque², Glaucius Oliva³ and Fernando Pavão^4,3

¹ Departamento de Química, Universidade Federal de São Carlos, CP 676, São Carlos, SP, Brazil
² Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
³ Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil
⁴ Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil

Abstract: Crude extracts of Rutales species were tested in vitro against the trypomastigote form of Trypanosoma cruzi at 4 mg/mL, and 20% of them showed significant activity (80%). Their inhibitory activity against the glycolytic enzyme GAPDH from T. cruzi has also been evaluated at the concentrations of 100 and 200 mg/mL. Additionally, the inhibitory activity of 13 purified coumarins were also assayed against T. cruzi-GAPDH. Chalepin was the most active substance with IC50 = 64 mM. The 3D structure of the complex chalepin-enzyme was elucidated by X-ray crystallography, revealing the architecture of the interactions between the inhibitor and the enzyme active site.