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

Type:	Artigo de Periódico
Title:	Design, synthesis, and biodistribution studies of new analogues of marine alkaloids: potent in vitro and in vivo fungicidal agents against Candida spp.
Authors:	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
Abstract:	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.
Subject:	Atividade antifúngica Candida albicans Alcalóides Candidíase intra-abdominal
language:	eng
metadata.dc.publisher.country:	Brasil
Publisher:	Universidade Federal de Minas Gerais
Publisher Initials:	UFMG
metadata.dc.publisher.department:	FAR - DEPARTAMENTO DE ALIMENTOS FAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICAS ICB - DEPARTAMENTO DE MICROBIOLOGIA
Rights:	Acesso Restrito
metadata.dc.identifier.doi:	10.1016/j.ejmech.2020.113048
URI:	http://hdl.handle.net/1843/41908
Issue Date:	15-Jan-2021
metadata.dc.url.externa:	https://www.sciencedirect.com/science/article/pii/S0223523420310205?via%3Dihub
metadata.dc.relation.ispartof:	European Journal of Medicinal Chemistry
Appears in Collections:	Artigo de Periódico

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