Anti-Candida albicans Activity of Thiazolylhydrazone Derivatives in Invertebrate and Murine Models

被引：22

作者：

Barreto Cruz, Lana Ivone ^{[1
]}

Finamore Lopes, Larissa Ferreira ^{[1
]}

Ribeiro, Felipe de Camargo ^{[2
]}

de Sa, Nivea Pereira ^{[1
,3
]}

Lino, Cleudiomar Inacio ^{[4
]}

Tharmalingam, Nagendran ^{[5
,6
]}

de Oliveira, Renata Barbosa ^{[4
]}

Rosa, Carlos Augusto ^{[1
]}

Mylonakis, Eleftherios ^{[5
,6
]}

Fuchs, Beth Burgwyn ^{[5
,6
]}

Johann, Susana ^{[1
]}

机构：

[1] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Microbiol, Ave Presidente Antonio Carlos 6627, BR-31270901 Belo Horizonte, MG, Brazil

[2] Inst Ciencia & Tecnol Sao Dos Jose Campos UNESP, Dept Biociencias & Diagnost Bucal, Av Francisco Jose Longe 777, BR-12245000 Sao Jose Dos Campos, SP, Brazil

[3] SUNY Stony Brook, Div Infect Dis, Dept Mol Genet & Microbiol, 150 Life Sci Bldg, Stony Brook, NY 11794 USA

[4] Univ Fed Minas Gerais, Dept Prod Farmaceut, Fac Farm, BR-31270901 Belo Horizonte, MG, Brazil

[5] Rhode Isl Hosp, Alpert Med Sch, Div Infect Dis, Providence, RI 02903 USA

[6] Brown Univ, Providence, RI 02903 USA

来源：

JOURNAL OF FUNGI | 2018年 / 4卷 / 04期

关键词：

Candida albicans; thiazolylhydrazone derivatives; antifungal; GALLERIA-MELLONELLA; RESISTANCE; MECHANISMS;

D O I：

10.3390/jof4040134

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Candidiasis is an opportunistic fungal infection with Candida albicans being the most frequently isolated species. Treatment of these infections is challenging due to resistance that can develop during therapy, and the limited number of available antifungal compounds. Given this situation, the aim of this study was to evaluate the antifungal activity of four thiazolylhydrazone compounds against C. albicans. Thiazolylhydrazone compounds 1, 2, 3, and 4 were found to exert antifungal activity, with MICs of 0.125-16.0 mu g/mL against C. albicans. The toxicity of the compounds was evaluated using human erythrocytes and yielded LC50 > 64 mu g/mL. The compounds were further evaluated using the greater wax moth Galleria mellonella as an in vivo model. The compounds prolonged larval survival when tested between 5 and 15 mg/kg, performing as well as fluconazole. Compound 2 was evaluated in murine models of oral and systemic candidiasis. In the oral model, compound 2 reduced the fungal load on the mouse tongue; and in the systemic model it reduced the fungal burden found in the kidney when tested at 10 mg/kg. These results show that thiazolylhydrazones are an antifungal towards C. albicans with in vivo efficacy.

引用

页数：14

共 30 条

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