Claudia M. Rezende
Federal University of Rio de Janeiro, Brazil
Title: Effect of coffee diterpenes against Leishmania amazonesis
Biography
Biography: Claudia M. Rezende
Abstract
Leishmaniasis is a public health problem in 98 countries and its therapy is based on pentavalent antimonials, pentamidine, amphotericin B and miltefosine. For all of them high toxicity, elevated cost and parasite resistance have been reported. Natural products are potential sources of novel active molecules that may provide structural template for drug discovery. Studies showed that coffee intake may be effective against heart and coronary disease, Parkinson's and Alzheimer's. Cafestol and kahweol (C&K) are two natural coffee diterpenes with antitumoral, antiinflammatory and antioxidant activities. The aim of this study was to evaluate the effect of C&K together and separately against Leishmania amazonensis. Cytotoxicity of C&K (1:1) for host cells was investigated by the XTT method. Our results demonstrated a CC50 of 26.9µg/mL. Besides, C&K presented an anti-L. amazonensis activity with an IC50 of 4.7µg/mL for promastigote forms, while for intracellular amastigotes the IC50 was 12.3µg/mL. The C&K selectivity index was 2.19. Our results showed that C&K does not induce nitric oxide (NO) production on macrophages infected with L. amazonensis, moreover, reduced 2.1-fold the NO production on IFN-γ and LPS-activated macrophages. To rule out a possible NO scavenger effect of C&K, a cell-free system was used with SNAP as a NO donor in the presence or not of C&K, and these drugs were not able to reduce NO levels. However, they increase 2.1-fold the production of reactive oxygen species in infected macrophages. Our data point C&K as promising substances for the development of a drug with leishmanicidal activity.