title: Anti-Candida targets and cytotoxicity of casuarinin isolated from Plinia cauliflora leaves in a bioactivity-guided study.
abstract: In addition to the bio-guided investigation of the antifungal activity of Plinia cauliflora leaves against different Candida species, the major aim of the present study was the search for targets on the fungal cell. The most active antifungal fraction was purified by chromatography and characterized by NMR and mass spectrometry. The antifungal activity was evaluated against five Candida strains according to referenced guidelines. Cytotoxicity against fibroblast cells was determined. The likely targets of Candida albicans cells were assessed through interactions with ergosterol and cell wall composition, porosity and architecture. The chemical major component within the most active antifungal fraction of P. cauliflora leaves identified was the hydrolysable tannin casuarinin. The cytotoxic concentration was higher than the antifungal one. The first indication of plant target on cellular integrity was suggested by the antifungal activity ameliorated when using an osmotic support. The most important target for the tannin fraction studied was suggested by ultrastructural analysis of yeast cell walls revealing a denser mannan outer layer and wall porosity reduced. It is possible to imply that P. cauliflora targeted the C. albicans cell wall inducing some changes in the architecture, notably the outer glycoprotein layer, affecting the cell wall porosity without alteration of the polysaccharide or protein level.
authors.affiliation: Department of Drugs and Medicines, School of Pharmaceutical Sciences, UNESP-Univ Estadual Paulista, Rodovia Araraquara-Jau, km 1, Araraquara, 14801-902 São Paulo, Brazil.
authors.forename: Tatiana M
authors.initials: TM
authors.lastname: Souza-Moreira
authors.forename: Juliana A
authors.initials: JA
authors.lastname: Severi
authors.forename: Keunsook
authors.initials: K
authors.lastname: Lee
authors.forename: Kanya
authors.initials: K
authors.lastname: Preechasuth
authors.forename: Emerson
authors.initials: E
authors.lastname: Santos
authors.forename: Neil A R
authors.initials: NA
authors.lastname: Gow
authors.forename: Carol A
authors.initials: CA
authors.lastname: Munro
authors.forename: Wagner
authors.initials: W
authors.lastname: Vilegas
authors.forename: Rosemeire C L R
authors.initials: RC
authors.lastname: Pietro
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002175:Candida / Q000145:classification / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy; D002473:Cell Wall / Q000187:drug effects*; D006023:Glycoproteins / Q000187:drug effects; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D027822:Myrtaceae / Q000378:metabolism*; D018515:Plant Leaves / Q000378:metabolism; D016062:Porosity / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D006023:Glycoproteins; D047348:Hydrolyzable Tannins; C472513:casuarinin