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

Jéssica Tauany Andrade; William Gustavo Lima; Jaqueline França Sousa; Aline Aparecida Saldanha; Nívea Pereira de sá; Jaqueline Maria Siqueira Ferreira; Fernanda Barbara Morais; Mayra Karla Prates Silva; Gustavo Henrique Ribeiro Viana; Susana Johann; Adriana Cristina Soares; Leonardo Allan Araújo; Simone Odília Antunes Fernandes; Valbert Nascimento Cardoso; Jaqueline Maria Siqueira Ferreira

Please use this identifier to cite or link to this item: http://hdl.handle.net/1843/41908

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DC Field	Value	Language
dc.creator	Jéssica Tauany Andrade	pt_BR
dc.creator	William Gustavo Lima	pt_BR
dc.creator	Jaqueline França Sousa	pt_BR
dc.creator	Aline Aparecida Saldanha	pt_BR
dc.creator	Nívea Pereira de sá	pt_BR
dc.creator	Jaqueline Maria Siqueira Ferreira	pt_BR
dc.creator	Fernanda Barbara Morais	pt_BR
dc.creator	Mayra Karla Prates Silva	pt_BR
dc.creator	Gustavo Henrique Ribeiro Viana	pt_BR
dc.creator	Susana Johann	pt_BR
dc.creator	Adriana Cristina Soares	pt_BR
dc.creator	Leonardo Allan Araújo	pt_BR
dc.creator	Simone Odília Antunes Fernandes	pt_BR
dc.creator	Valbert Nascimento Cardoso	pt_BR
dc.creator	Jaqueline Maria Siqueira Ferreira	pt_BR
dc.date.accessioned	2022-05-23T22:30:38Z	-
dc.date.available	2022-05-23T22:30:38Z	-
dc.date.issued	2021-01-15	-
dc.citation.volume	210	pt_BR
dc.citation.spage	1	pt_BR
dc.citation.epage	15	pt_BR
dc.identifier.doi	10.1016/j.ejmech.2020.113048	pt_BR
dc.identifier.issn	0223-5234	pt_BR
dc.identifier.uri	http://hdl.handle.net/1843/41908	-
dc.description.resumo	Invasive 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.	pt_BR
dc.description.sponsorship	CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico	pt_BR
dc.description.sponsorship	FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais	pt_BR
dc.description.sponsorship	CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior	pt_BR
dc.language	eng	pt_BR
dc.publisher	Universidade Federal de Minas Gerais	pt_BR
dc.publisher.country	Brasil	pt_BR
dc.publisher.department	FAR - DEPARTAMENTO DE ALIMENTOS	pt_BR
dc.publisher.department	FAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICAS	pt_BR
dc.publisher.department	ICB - DEPARTAMENTO DE MICROBIOLOGIA	pt_BR
dc.publisher.initials	UFMG	pt_BR
dc.relation.ispartof	European Journal of Medicinal Chemistry	pt_BR
dc.rights	Acesso Restrito	pt_BR
dc.subject	Antifungal activity	pt_BR
dc.subject	Candida albicans	pt_BR
dc.subject	Alkaloids	pt_BR
dc.subject	Biofilm	pt_BR
dc.subject	99mTc radiolabeled alkaloids	pt_BR
dc.subject	Intra-abdominal candidiasis	pt_BR
dc.subject.other	Atividade antifúngica	pt_BR
dc.subject.other	Candida albicans	pt_BR
dc.subject.other	Alcalóides	pt_BR
dc.subject.other	Candidíase intra-abdominal	pt_BR
dc.title	Design, synthesis, and biodistribution studies of new analogues of marine alkaloids: potent in vitro and in vivo fungicidal agents against Candida spp.	pt_BR
dc.type	Artigo de Periódico	pt_BR
dc.url.externa	https://www.sciencedirect.com/science/article/pii/S0223523420310205?via%3Dihub	pt_BR
Appears in Collections:	Artigo de Periódico

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