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噻唑基腙衍生物在无脊椎动物和小鼠模型中的抗活性

Anti- Activity of Thiazolylhydrazone Derivatives in Invertebrate and Murine Models.

作者信息

Cruz Lana Ivone Barreto, Lopes Larissa Ferreira Finamore, de Camargo Ribeiro Felipe, de Sá Nívea Pereira, Lino Cleudiomar Inácio, Tharmalingam Nagendran, de Oliveira Renata Barbosa, Rosa Carlos Augusto, Mylonakis Eleftherios, Fuchs Beth Burgwyn, Johann Susana

机构信息

Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Presidente Antônio Carlos, 6627, Pampulha, Belo Horizonte-Minas Gerais 31270-901, Brasil.

Departamento de Biociências e Diagnóstico Bucal, Instituto de Ciência e Tecnologia de São José dos Campos-UNESP, Av. Francisco José Longe, 777, Jardim São Dimas, São José dos Campos-São Paulo 12245-000, Brasil.

出版信息

J Fungi (Basel). 2018 Dec 12;4(4):134. doi: 10.3390/jof4040134.

Abstract

Candidiasis is an opportunistic fungal infection with 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 . Thiazolylhydrazone compounds , , , and were found to exert antifungal activity, with MICs of 0.125⁻16.0 μg/mL against . . The toxicity of the compounds was evaluated using human erythrocytes and yielded LC > 64 μg/mL. The compounds were further evaluated using the greater wax moth as an in vivo model. The compounds prolonged larval survival when tested between 5 and 15 mg/kg, performing as well as fluconazole. Compound was evaluated in murine models of oral and systemic candidiasis. In the oral model, compound 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 with in vivo efficacy.

摘要

念珠菌病是一种机会性真菌感染, 是最常分离出的菌种。由于治疗期间可能产生耐药性以及可用抗真菌化合物数量有限,这些感染的治疗具有挑战性。鉴于这种情况,本研究的目的是评估四种噻唑基腙化合物对 的抗真菌活性。发现噻唑基腙化合物 、 、 和 具有抗真菌活性,对 的最低抑菌浓度为0.125⁻16.0μg/mL。使用人红细胞评估了这些化合物的毒性,其半数致死浓度>64μg/mL。使用大蜡螟作为体内模型对这些化合物进行了进一步评估。当在5至15mg/kg之间进行测试时,这些化合物延长了幼虫的存活时间,效果与氟康唑相当。化合物 在口腔和全身性念珠菌病的小鼠模型中进行了评估。在口腔模型中,化合物 降低了小鼠舌头上的真菌载量;在全身模型中,当以10mg/kg进行测试时,它降低了肾脏中的真菌负荷。这些结果表明,噻唑基腙对 具有抗真菌作用且具有体内疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1209/6308944/032cb24f7608/jof-04-00134-g001.jpg

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