Design, synthesis, biological activity and structure-activity relationship studies of chalcone derivatives as potential anti-Candida agents

被引：45

作者：

Andrade, Jessica T. ^{[1
]}

Santos, Felipe R. S. ^{[1
,2
]}

Lima, William G. ^{[1
]}

Sousa, Carla D. F. ^{[1
]}

Oliveira, Lohanna S. F. M. ^{[3
]}

Ribeiro, Rosy I. M. A. ^{[3
]}

Gomes, Ana J. P. S. ^{[4
]}

Araujo, Marcelo G. F. ^{[5
]}

Villar, Jose A. F. P. ^{[2
]}

Ferreira, Jaqueline M. S. ^{[1
]}

机构：

[1] Univ Fed Sao Joao del Rei UFSJ, Lab Microbiol Med, Campus Ctr Oeste Dona Lindu, Divinopolis, MG, Brazil

[2] Univ Fed Sao Joao del Rei UFSJ, Lab Sintese Organ & Nanoestruturas, Campus Ctr Oeste Dona Lindu, Divinopolis, MG, Brazil

[3] Univ Fed Sao Joao del Rei UFSJ, Lab Patol Expt, Campus Ctr Oeste Dona Lindu, Divinopolis, MG, Brazil

[4] Univ Fed Sao Joao del Rei UFSJ, Lab Desenvolvimento Farmacotecn, Campus Ctr Oeste Dona Lindu, Divinopolis, MG, Brazil

[5] Univ Fed Sao Joao del Rei UFSJ, Lab Farmacol, Campus Ctr Oeste Dona Lindu, Divinopolis, MG, Brazil

来源：

JOURNAL OF ANTIBIOTICS | 2018年 / 71卷 / 08期

关键词：

ANTIFUNGAL EVALUATION; MECHANISM; ANTIBACTERIAL; DISCOVERY; ANALOGS; SERIES;

D O I：

10.1038/s41429-018-0048-9

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Vulvovaginal candidiasis (VVC) affects millions of women around the world every year. Candida albicans is the most frequently isolated pathogen in women and its rapid ability to develop resistance to first and second line therapies has boosted the search for new and effective antifungal agents. In this study, we show the in vitro anti-Candida activity of fifteen synthetic chalcone analogs and their antifungal potential in an in vivo model of VVC. Chalcone 12 showed potent antifungal effects, being able to inhibit the growth of Candida spp. at a concentration of 15.6 mu g mL(-1). In addition, mechanism of action studies have indicated the ergosterol fungal membrane as the target of this compound. Despite a considerable antifungal activity, the chalcone 12 showed high cytotoxicity in kidney cells lineages. Moreover, this compound was able to reduce Candida-associated virulence, impairing yeast-hyphal transition in C. albicans. An in vivo model of VVC showed that chalcone 12 significantly reduces the fungal load. Taken together, these findings showed that the chalcone 12 is a potent anti-Candida agent in vitro beyond of contribute to improve the fungal infection in a model of CVV. However, it showed low selectivity and high toxicity, suggesting molecular modifications to minimize these proprieties.

引用

页码：702 / 712

页数：11

共 46 条

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