Heterocycle thiazole compounds exhibit antifungal activity through increase in the production of reactive oxygen species in Cryptococcus neoformans-Cryptococcus gatti species complex

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dc.creatorNívea Pereira de Sá
dc.creatorCaroline Miranda de Lima
dc.creatorCleudiomar Inácio Lino
dc.creatorPaulo Jorge Sanches Barbeira
dc.creatorLudmila de Matos Baltazar
dc.creatorDaniel Assis Santos
dc.creatorRenata Barbosa de Oliveira
dc.creatorEleftherios Mylonakis
dc.creatorBeth Burgwyn Fuchs
dc.creatorSusana Johann
dc.date.accessioned2024-04-19T12:09:05Z
dc.date.accessioned2025-09-09T01:17:08Z
dc.date.available2024-04-19T12:09:05Z
dc.date.issued2017
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
dc.description.sponsorshipFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.identifier.doihttps://doi.org/10.1128/aac.02700-16
dc.identifier.issn1098-6596
dc.identifier.urihttps://hdl.handle.net/1843/67449
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofAntimicrobial Agents and Chemotherapy
dc.rightsAcesso Restrito
dc.subjectAntimicoticos
dc.subjectFungos
dc.subjectCompostos heterociclicos
dc.subjectAtividade antifúngica
dc.subjectTremellales
dc.subjectMicoses sistêmicas
dc.subject.otherAntifungal
dc.subject.otherAntioxidant
dc.subject.otherCryptococcus
dc.subject.otherThiazoles
dc.subject.otherROS
dc.subject.otherRNS
dc.titleHeterocycle thiazole compounds exhibit antifungal activity through increase in the production of reactive oxygen species in Cryptococcus neoformans-Cryptococcus gatti species complex
dc.typeArtigo de periódico
local.citation.issue8
local.citation.volume61
local.description.resumoHuman cryptococcosis can occur as a primary or opportunistic infection and develops as an acute, subacute, or chronic systemic infection involving different organs of the host. Given the limited therapeutic options and the occasional resistance to fluconazole, there is a need to develop novel drugs for the treatment of cryptococcosis. In this report, we describe promising thiazole compounds 1, 2, 3, and 4 and explore their possible modes of action against Cryptococcus. To this end, we show evidence of interference in the Cryptococcus antioxidant system. The tested compounds exhibited MICs ranging from 0.25 to 2 μg/ml against Cryptococcus neoformans strains H99 and KN99α. Interestingly, the knockout strains for Cu oxidase and sarcosine oxidase were resistant to thiazoles. MIC values of thiazole compounds 1, 2, and 4 against these mutants were higher than for the parental strain. After the treatment of C. Neoformans ATCC 24067 (or C. deneoformans) and C. Gattii strain L27/01 (or C. deuterogattii) with thiazoles, we verified an increase in intracellular reactive oxygen species (ROS). Also, we verified the synergistic interactions among thiazoles and menadione, which generates superoxides, with fractional inhibitory concentrations (FICs) equal to 0.1874, 0.3024, 0.25, and 0.25 for the thiazole compounds 1, 2, 3, and 4, respectively. In addition, thiazoles exhibited antagonistic interactions with parasulphonatephenyl porphyrinato ferrate III (FeTPPS). Thus, in this work, we showed that the action of these thiazoles is related to an interference with the antioxidant system. These findings suggest that oxidative stress may be primarily related to the accumulation of superoxide radicals.
local.identifier.orcidhttps://orcid.org/0000-0002-0770-8680
local.identifier.orcidhttps://orcid.org/0000-0002-4255-3047
local.identifier.orcidhttps://orcid.org/0000-0002-1108-5666
local.identifier.orcidhttps://orcid.org/0000-0001-5884-2567
local.identifier.orcidhttps://orcid.org/0000-0002-4624-0777
local.identifier.orcidhttps://orcid.org/0000-0001-8068-1720
local.publisher.countryBrasil
local.publisher.departmentFAR - DEPARTAMENTO DE PRODUTOS FARMACÊUTICOS
local.publisher.departmentICB - DEPARTAMENTO DE MICROBIOLOGIA
local.publisher.departmentICX - DEPARTAMENTO DE QUÍMICA
local.publisher.initialsUFMG
local.url.externahttps://journals.asm.org/doi/10.1128/aac.02700-16

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