Design, synthesis, and biodistribution studies of new analogues of marine alkaloids: potent in vitro and in vivo fungicidal agents against Candida spp.

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dc.creatorJéssica Tauany Andrade
dc.creatorWilliam Gustavo Lima
dc.creatorJaqueline França Sousa
dc.creatorAline Aparecida Saldanha
dc.creatorNívea Pereira de sá
dc.creatorJaqueline Maria Siqueira Ferreira
dc.creatorFernanda Barbara Morais
dc.creatorMayra Karla Prates Silva
dc.creatorGustavo Henrique Ribeiro Viana
dc.creatorSusana Johann
dc.creatorAdriana Cristina Soares
dc.creatorLeonardo Allan Araújo
dc.creatorSimone Odília Antunes Fernandes
dc.creatorValbert Nascimento Cardoso
dc.creatorJaqueline Maria Siqueira Ferreira
dc.date.accessioned2022-05-23T22:30:38Z
dc.date.accessioned2025-09-09T00:01:17Z
dc.date.available2022-05-23T22:30:38Z
dc.date.issued2021-01-15
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.doi10.1016/j.ejmech.2020.113048
dc.identifier.issn0223-5234
dc.identifier.urihttps://hdl.handle.net/1843/41908
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofEuropean Journal of Medicinal Chemistry
dc.rightsAcesso Restrito
dc.subjectAtividade antifúngica
dc.subjectCandida albicans
dc.subjectAlcalóides
dc.subjectCandidíase intra-abdominal
dc.subject.otherAntifungal activity
dc.subject.otherCandida albicans
dc.subject.otherAlkaloids
dc.subject.otherBiofilm
dc.subject.other99mTc radiolabeled alkaloids
dc.subject.otherIntra-abdominal candidiasis
dc.titleDesign, synthesis, and biodistribution studies of new analogues of marine alkaloids: potent in vitro and in vivo fungicidal agents against Candida spp.
dc.typeArtigo de periódico
local.citation.epage15
local.citation.spage1
local.citation.volume210
local.description.resumoInvasive candidiasis, such as intra-abdominal candidiasis (IAC), is a significant cause of morbidity and mortality worldwide. IAC is still poorly understood, and its treatment represents a challenge for public health. In this study, we showed the in vitro anti-Candida activity of four alkaloid synthetic derivatives and their antifungal potential in a murine model of IAC. The biological effects of alkaloids were evaluated against Candida spp. through the determination of the minimum inhibitory concentration (MIC). For the alkaloids that showed antifungal activity, the fungicidal concentration, time-kill curve, synergism with azoles and polyenes, phenotypic effects, and the effect against virulence factors were also determined. The most active alkaloids were selected for in vivo assays. The compounds 6a and 6b were active against C. albicans, C. glabrata, and C. tropicalis (MIC 7.8 μg/mL) and showed promising antifungal activity against C. krusei (MIC 3.9 μg/mL). The compound 6a presented a potent fungicidal effect in vitro, eliminating the yeast C. albicans after 8 h of incubation at MIC. An important in vitro synergistic effect with ketoconazole was observed for these two alkaloids. They also induced the lysis of fungal cells by binding to the ergosterol of the membrane. Besides that, 6a and 6b were able to reduce yeast–to-hyphal transition in C. albicans, as well as inhibit the biofilm formation of this pathogen. In the in vivo assay, the compound 6a did not show acute toxicity and was mainly absorbed by the liver, spleen, and lung after a parenteral administration. Also, this analogue significantly reduced the fungal load of C. albicans on the kidney and spleen of animals with IAC. Therefore, these results showed that the compound 6a is a potent anti-Candida agent in vitro and in vivo.
local.publisher.countryBrasil
local.publisher.departmentFAR - DEPARTAMENTO DE ALIMENTOS
local.publisher.departmentFAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICAS
local.publisher.departmentICB - DEPARTAMENTO DE MICROBIOLOGIA
local.publisher.initialsUFMG
local.url.externahttps://www.sciencedirect.com/science/article/pii/S0223523420310205?via%3Dihub

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