title: TTAS a new stilbene derivative that induces apoptosis in Leishmania infantum.
abstract: Leishmania parasites are able to undergo apoptosis (programmed cell death), similarly to mammalian cells. Recently it was demonstrated in vitro the anti-leishmanial effect of some natural and synthetic stilbenoids including resveratrol and piceatannol. In this study we evaluated the Leishmanicidal activity of a pool of stilbene derivatives which had previously shown high apoptotic efficacy against neoplastic cells. All the compounds tested were capable to decrease the parasite viability in a dose-dependent manner. Trans-stilbenes proved to be markedly more effective than cis-isomers. This was different from that observed in tumor cells in which cis-stilbenes were more potent cytotoxic agents. Trans-3,4',5-trimethoxy-3'-amino-stilbene (TTAS) was the most active stilbene showing in Leishmania infantum a LD(50) value of 2.6 μg/mL. In contrast TTAS showed a low toxicity when tested on normal hemopoietic cells. This compound induced apoptosis in parasites by disrupting the mitochondrial membrane potential. Moreover it shows the ability to block Leishmania parasites in G(2)-M phase of cell cycle in agreement with the data obtained by affinity chromatography that identify tubulin as the putative target of TTAS. In conclusion, our results indicate that some stilbene derivatives are highly effective as anti-leishmanial agents and TTAS represents a pro-apoptotic agent in Leishmania parasites that merit further in vivo investigation.
authors.affiliation: Department of Health Promotion Sciences, Section of Infectious Diseases, University of Palermo, Via del Vespro 129, 90127 Palermo, Italy. mtolomeo@hotmail.com
authors.forename: Manlio
authors.initials: M
authors.lastname: Tolomeo
authors.forename: Marinella
authors.initials: M
authors.lastname: Roberti
authors.forename: Leonardo
authors.initials: L
authors.lastname: Scapozza
authors.forename: Chiara
authors.initials: C
authors.lastname: Tarantelli
authors.forename: Elisa
authors.initials: E
authors.lastname: Giacomini
authors.forename: Lucina
authors.initials: L
authors.lastname: Titone
authors.forename: Laura
authors.initials: L
authors.lastname: Saporito
authors.forename: Paola
authors.initials: P
authors.lastname: Di Carlo
authors.forename: Claudia
authors.initials: C
authors.lastname: Colomba
mesh_terms: D017304:Annexin A5; D000967:Antimony Sodium Gluconate / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D055014:Granulocyte-Macrophage Progenitor Cells / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D018314:Leishmania infantum / Q000166:cytology / Q000187:drug effects*; D007928:Lethal Dose 50; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D014404:Tubulin / Q000187:drug effects
chemical_list: C476602:3,4',5-trimethoxy-3'-aminostilbene; D017304:Annexin A5; D000981:Antiprotozoal Agents; D013267:Stilbenes; D014404:Tubulin; D000967:Antimony Sodium Gluconate