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 Pavão3,4
1Departamento de Química, Universidade Federal
de São Carlos, CP 676, São Carlos, SP, Brazil; 2Faculdade
de Ciências Farmacêuticas de Ribeirão Preto, Universidade
de São Paulo, Ribeirão Preto, SP, Brazil; 3Instituto de
Física de São Carlos, Universidade de São Paulo,
São Carlos, SP, Brazil; 4Instituto 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.
*Lecture presented at the 22nd IUPAC International
Symposium on the Chemistry of Natural Products, São Carlos, Brazil,
3-8 September 2000. Other presentations are published in this issue,
pp. 549-626.
**Corresponding
author
