Leishmanicidal Effect of Synthetic trans-Resveratrol Analogs

Background Stilbene-based compounds show antitumoral, antioxidant, antihistaminic, anti-inflammatory and antimicrobial activities. Here, we evaluated the effect of the trans-resveratrol analogs, pterostilbene, piceatannol, polydatin and oxyresveratrol, against Leishmania amazonensis. Methodology/Principal Findings Our results demonstrated a low murine macrophage cytotoxicity of all four analogs. Moreover, pterostilbene, piceatannol, polydatin and oxyresveratrol showed an anti-L. amazonensis activity with IC50 values of 18 mu M, 65 mu M, 95 mu M and 65 mu M for promastigotes, respectively. For intracellular amastigotes, the IC50 values of the analogs were 33.2 mu M, 45 mu M, 29 mu M and 30.5 mu M, respectively. Among the analogs assayed only piceatannol altered the cell cycle of the parasite, increasing 5-fold the cells in the Sub-G0 phase and decreasing 1.7-fold the cells in the G0-G1 phase. Piceatannol also changed the parasite mitochondrial membrane potential (Delta psi m) and increased the number of annexin-V positive promastigotes, which suggests incidental death. Conclusion/Significance Among the analogs tested, piceatannol, which is a metabolite of resveratrol, was the more promising candidate for future studies regarding treatment of leishmaniasis.