title: Nimesulide inhibits pathogenic fungi: PGE2-dependent mechanisms.
abstract: Certain non-steroidal anti-inflammatory drugs can inhibit fungal growth, fungal prostaglandin E2 production, and enzyme activation. This study aims to investigate the antifungal effect of nimesulide against pathogenic filamentous fungi and yeast. The experiments detailed below were also designed to investigate whether the action is dependent on E2 fungal prostaglandins. Our data showed that nimesulide exhibited potent antifungal activity, mainly against Trichophyton mentagrophytes (ATCC 9533) and Cryptococcus neoformans with MIC values of 2 and 62 μg/mL, respectively. This drug was also able to inhibit the growth of clinic isolates of filamentous fungi, such as Aspergillus fumigatus, and dermatophytes, such as T. rubrum, T. mentagrophytes, Epidermophyton floccosum, Microsporum canis, and M. gypseum, with MIC values ranging from 112 to 770 μg/mL. Our data also showed that the inhibition of fungal growth by nimesulide was mediated by a mechanism dependent on PGE2, which led to the inhibition of essential fungal enzymes. Thus, we concluded that nimesulide exerts a fungicidal effect against pathogenic filamentous fungi and yeast, involving the inhibition of fungal prostaglandins and fungal enzymes important to the fungal growth and colonization.
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Pará/UFPA, Rua Augusto Corrêa, 01, Bairro Guamá, Belém, PA, 66075-110, Brazil.
authors.forename: Rafaelle Fonseca
authors.initials: RF
authors.lastname: de Matos
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Pará/UFPA, Rua Augusto Corrêa, 01, Bairro Guamá, Belém, PA, 66075-110, Brazil.
authors.forename: Lúcia Carla Vasconcelos
authors.initials: LCV
authors.lastname: Mendonça
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Pará/UFPA, Rua Augusto Corrêa, 01, Bairro Guamá, Belém, PA, 66075-110, Brazil.
authors.forename: Kaira Geiliane
authors.initials: KG
authors.lastname: da Silva Souza
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Pará/UFPA, Rua Augusto Corrêa, 01, Bairro Guamá, Belém, PA, 66075-110, Brazil.
authors.forename: Adriana Aparecida Durães
authors.initials: AAD
authors.lastname: Fonseca
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Pará/UFPA, Rua Augusto Corrêa, 01, Bairro Guamá, Belém, PA, 66075-110, Brazil.
authors.forename: Elaine Mirla Souza
authors.initials: EMS
authors.lastname: Costa
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Pará/UFPA, Rua Augusto Corrêa, 01, Bairro Guamá, Belém, PA, 66075-110, Brazil.
authors.forename: Marcus Vinicius Dias
authors.initials: MVD
authors.lastname: de Lima
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Pará/UFPA, Rua Augusto Corrêa, 01, Bairro Guamá, Belém, PA, 66075-110, Brazil.
authors.forename: José Maria Dos Santos
authors.initials: JMDS
authors.lastname: Vieira
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Pará/UFPA, Rua Augusto Corrêa, 01, Bairro Guamá, Belém, PA, 66075-110, Brazil.
authors.forename: Mioni Thielli Figueiredo Magalhães
authors.initials: MTFM
authors.lastname: de Brito
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Programa de Pós-graduação Neurociências e Biologia Celular, Programa de Pós-graduação em Química Medicinal e Modelagem Molecular, Instituto de Ciências da Saúde, Universidade Federal do Pará/UFPA, Belém, PA, 66075-110, Brazil. martachagas2@yahoo.com.br.
authors.forename: Marta Chagas
authors.initials: MC
authors.lastname: Monteiro
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D003883:Arthrodermataceae / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008826:Microbial Sensitivity Tests; D013449:Sulfonamides / Q000494:pharmacology*; D014249:Trichophyton / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D013449:Sulfonamides; D015232:Dinoprostone; C012655:nimesulide