title: Synergistic effect of pedalitin and amphotericin B against Cryptococcus neoformans by in vitro and in vivo evaluation.
abstract: Cryptococcosis is an opportunistic fungal infection responsible for high morbidity and mortality in immunocompromised patients. Combination of antifungal substances is a promising way to increase the percentage of successful treatment. Pedalitin (PED) is a natural substance obtained from Pterogyne nitens. The aim of this study was to verify the efficacy of PED alone and in combination with amphotericin B (AmB) in vitro and in vivo against Cryptococcus spp. In the in vitro assay, minimum inhibitory concentrations (MICs) of 0.125 mg/L for AmB and 3.9 mg/L for PED were found when the substances were tested alone, whilst in the combination treatment the active concentration of both decreased, with MICs of 0.03 mg/L for AmB and 1 mg/L for PED. In the survival assay, fungal burden study and histopathological assays it was possible to study the efficacy of the substances alone and in combination. The efficacy of combination therapy was considered better than monotherapy as evaluated in a Galleria mellonella model and a murine model. Thus, the combination of PED and AmB is an interesting alternative for anticryptococcal fungal treatment. Moreover, a correlation was observed between the invertebrate and murine models for this antifungal treatment combination.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Araraquara, Universidade Estadual Paulista (UNESP), Departamento de Análises Clínicas, Laboratório de Micologia Clínica, Araraquara, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Sangalli-Leite
authors.affiliation: Faculdade de Ciências Farmacêuticas de Araraquara, Universidade Estadual Paulista (UNESP), Departamento de Análises Clínicas, Laboratório de Micologia Clínica, Araraquara, Brazil.
authors.forename: Liliana
authors.initials: L
authors.lastname: Scorzoni
authors.affiliation: Faculdade de Ciências Farmacêuticas de Araraquara, Universidade Estadual Paulista (UNESP), Departamento de Análises Clínicas, Laboratório de Micologia Clínica, Araraquara, Brazil.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Alves de Paula E Silva
authors.affiliation: Faculdade de Ciências Farmacêuticas de Araraquara, Universidade Estadual Paulista (UNESP), Departamento de Análises Clínicas, Laboratório de Micologia Clínica, Araraquara, Brazil.
authors.forename: Julhiany de Fátima
authors.initials: JF
authors.lastname: da Silva
authors.affiliation: Faculdade de Ciências Farmacêuticas de Araraquara, Universidade Estadual Paulista (UNESP), Departamento de Análises Clínicas, Laboratório de Micologia Clínica, Araraquara, Brazil.
authors.forename: Haroldo Cesar
authors.initials: HC
authors.lastname: de Oliveira
authors.affiliation: Faculdade de Ciências Farmacêuticas de Araraquara, Universidade Estadual Paulista (UNESP), Departamento de Análises Clínicas, Laboratório de Micologia Clínica, Araraquara, Brazil.
authors.forename: Junya
authors.initials: J
authors.lastname: de Lacorte Singulani
authors.affiliation: Faculdade de Ciências Farmacêuticas de Araraquara, Universidade Estadual Paulista (UNESP), Departamento de Análises Clínicas, Laboratório de Micologia Clínica, Araraquara, Brazil.
authors.forename: Fernanda Patrícia
authors.initials: FP
authors.lastname: Gullo
authors.affiliation: Faculdade de Ciências Farmacêuticas de Araraquara, Universidade Estadual Paulista (UNESP), Departamento de Análises Clínicas, Laboratório de Micologia Clínica, Araraquara, Brazil.
authors.forename: Rosangela
authors.initials: R
authors.lastname: Moraes da Silva
authors.affiliation: Instituto de Química, Universidade Estadual Paulista (UNESP), Araraquara, Brazil.
authors.forename: Luis Octávio
authors.initials: LO
authors.lastname: Regasini
authors.affiliation: Instituto de Química, Universidade Estadual Paulista (UNESP), Araraquara, Brazil.
authors.forename: Dulce Helena
authors.initials: DH
authors.lastname: Siqueira da Silva
authors.affiliation: Instituto de Química, Universidade Estadual Paulista (UNESP), Araraquara, Brazil.
authors.forename: Vanderlan
authors.initials: V
authors.lastname: da Silva Bolzani
authors.affiliation: Faculdade de Ciências Farmacêuticas de Araraquara, Universidade Estadual Paulista (UNESP), Departamento de Análises Clínicas, Laboratório de Micologia Clínica, Araraquara, Brazil.
authors.forename: Ana Marisa
authors.initials: AM
authors.lastname: Fusco-Almeida
authors.affiliation: Faculdade de Ciências Farmacêuticas de Araraquara, Universidade Estadual Paulista (UNESP), Departamento de Análises Clínicas, Laboratório de Micologia Clínica, Araraquara, Brazil. Electronic address: giannini@fcfar.unesp.br.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Soares Mendes-Giannini
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015169:Colony Count, Microbial; D003453:Cryptococcosis / Q000188:drug therapy / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000187:drug effects*; D004195:Disease Models, Animal; D004357:Drug Synergism; D047309:Flavones / Q000008:administration & dosage / Q000494:pharmacology*; D007915:Lepidoptera; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D047309:Flavones; C510777:pedalitin; D000666:Amphotericin B
keywords: Amphotericin B; Chequerboard; Cryptococcus neoformans; Galleria mellonella; Pedalitin