title: Selective photoinactivation of Histoplasma capsulatum by water-soluble derivatives chalcones.
abstract: Histoplasmosis is a respiratory and systemic disease caused by the dimorphic fungus Histoplasma capsulatum. The clinical features may vary from asymptomatic infections to disseminated severe form depending of patient immunity. The treatment of histoplasmosis can be performed with itraconazole, fluconazole, and in the disseminated forms is used amphotericin B. However, the critical side effects of amphotericin B, the cases of itraconazole therapy failure and the appearance of fluconozole-resistant strains makes necessary the search of new strategies to treat this disease. Antimicrobial photodynamic therapy (aPDT) seems to be a potential candidate once have been show efficacy to inhibit others dimorphic fungi. Although the photosensitizer (PS) chalcone aggregates in biological medium, it has antifungal activity and show a high quantum yield of ROS formation. So, the aim of this study was to obtain the experimental parameters to achieve an acceptable selective chalcone water-soluble derivatives photoinactivation of H. capsulatum comparing with fibroblastic and keratinocytes cells which are the constituents of some potential host tissues. Yeast and cells were incubated with the same chalchones concentrations and short incubation time followed by irradiation with equal dose of light. The best conditions to kill H. capsulatum selectively were very low photosensitizers concentration (1.95μgmL-1) incubated by 15min and irradiated with LED 450nm with 24Jcm-2. Key words: chalcone, Histoplasma capsulatum, aPDT, selectivity.
authors.affiliation: Biociências e Biotecnologia Aplicada a Farmácia/Núcleo Proteomica, Universidade Estadual Paulista, Araraquara-SP, Brazil.
authors.forename: Wanessa C M A
authors.initials: WCMA
authors.lastname: Melo
authors.affiliation: Instituto de Biociências, Letras e Ciências Exatas, Universidade Estadual Paulista, São José do Rio-SP, Brazil.
authors.forename: Mariana Bastos Dos
authors.initials: MBD
authors.lastname: Santos
authors.affiliation: Instituto de Biociências, Letras e Ciências Exatas, Universidade Estadual Paulista, São José do Rio-SP, Brazil.
authors.forename: Beatriz de Carvalho
authors.initials: BC
authors.lastname: Marques
authors.affiliation: Instituto de Biociências, Letras e Ciências Exatas, Universidade Estadual Paulista, São José do Rio-SP, Brazil.
authors.forename: Luis Octávio
authors.initials: LO
authors.lastname: Regasini
authors.affiliation: Biociências e Biotecnologia Aplicada a Farmácia/Núcleo Proteomica, Universidade Estadual Paulista, Araraquara-SP, Brazil.
authors.forename: Maria José Soares Mendes
authors.initials: MJSM
authors.lastname: Giannini
authors.affiliation: Biociências e Biotecnologia Aplicada a Farmácia/Núcleo Proteomica, Universidade Estadual Paulista, Araraquara-SP, Brazil. Electronic address: almeidaf@fcfar.unesp.br.
authors.forename: Ana Marisa Fusco
authors.initials: AMF
authors.lastname: Almeida
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D047188:Chalcones / Q000008:administration & dosage*; D004203:Disinfection / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D006658:Histoplasma / Q000187:drug effects* / Q000528:radiation effects*; D008027:Light; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage; D011829:Radiation Dosage; D012995:Solubility; D016896:Treatment Outcome; D014867:Water / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D047188:Chalcones; D017319:Photosensitizing Agents; D014867:Water
keywords: Chalcone; Histoplasma capsulatum; Selectivity; aPDT