title: Anti-leishmanial activity of plant-derived acridones, flavaglines, and sulfur-containing amides.
abstract: Visceral and cutaneous leishmaniases are an important public health problem in endemic geographic regions in 88 countries worldwide, with around 12 million infected people. Treatment options are limited due to toxicity and teratogenicity of the available drugs, response problems in HIV/Leishmania co-infections, and upcoming resistances. In this study, we investigated the anti-leishmanial activity of 13 plant-derived compounds in vitro aiming to find new drug candidates. Toxicity of the compounds was evaluated in human primary hepatocytes, and hemolytic activity was examined in freshly isolated erythrocytes. Two acridones, 5-hydroxynoracronycine and yukocitrine, two flavaglines, aglafoline and rocaglamide, and the sulfur-containing amide methyldambullin showed promising anti-leishmanial activities with 50% effective concentrations (EC50s) of 34.84, 29.76, 7.45, 16.45, and 6.29 μM, respectively. Hepatotoxic activities of 5-hydroxynoracronycine, yukocitrine, and methyldambullin were significantly lower compared to miltefosine and lower or equal compared to artesunate, whereas the ones of rocaglamide and aglafoline were slightly higher compared to miltefosine and significantly higher compared to artesunate. None of the compounds showed hemolytic activity.
authors.affiliation: Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Astelbauer
authors.forename: Andreas
authors.initials: A
authors.lastname: Obwaller
authors.forename: Adriane
authors.initials: A
authors.lastname: Raninger
authors.forename: Brigitte
authors.initials: B
authors.lastname: Brem
authors.forename: Harald
authors.initials: H
authors.lastname: Greger
authors.forename: Michael
authors.initials: M
authors.lastname: Duchêne
authors.forename: Walther
authors.initials: W
authors.lastname: Wernsdorfer
authors.forename: Julia
authors.initials: J
authors.lastname: Walochnik
mesh_terms: D000166:Acridines / Q000494:pharmacology / Q000592:standards; D054831:Acridones; D000577:Amides / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000592:standards; D019659:Asteraceae; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D018314:Leishmania infantum / Q000187:drug effects* / Q000254:growth & development; D007896:Leishmaniasis / Q000188:drug therapy*; D019684:Magnoliopsida; D029582:Meliaceae; D008517:Phytotherapy / Q000379:methods* / Q000592:standards; D010936:Plant Extracts / Q000494:pharmacology* / Q000592:standards; D028321:Plant Preparations / Q000494:pharmacology / Q000592:standards; D027821:Rutaceae; D041901:Stemonaceae; D013455:Sulfur / Q000494:pharmacology / Q000592:standards
chemical_list: D000166:Acridines; D054831:Acridones; D000577:Amides; D000981:Antiprotozoal Agents; D010936:Plant Extracts; D028321:Plant Preparations; C041300:acridone; D013455:Sulfur