α-咔啉衍生物对……的筛选及抗真菌活性
Screening and Antifungal Activity of a -Carboline Derivative against and .
作者信息
Cruz Kátia Santana, Lima Emerson Silva, da Silva Marcia de Jesus Amazonas, de Souza Erica Simplício, Montoia Andreia, Pohlit Adrian Martin, de Souza João Vicente Braga
机构信息
Programa de Pós-Graduação da Rede de Biodiversidade e Biotecnologia da Amazônia Legal-Bionorte, Manaus, Amazonas, Brazil.
Universidade Federal do Amazonas, Manaus, Amazonas, Brazil.
出版信息
Int J Microbiol. 2019 Jan 22;2019:7157845. doi: 10.1155/2019/7157845. eCollection 2019.
BACKGROUND
Cryptococcosis is a fungal disease of bad prognosis due to its pathogenicity and the toxicity of the drugs used for its treatment. The aim of this study was to investigate the medicinal potential of carbazole and -carboline alkaloids and derivatives against and .
METHODS
MICs were established in accordance with the recommendations of the Clinical and Laboratory Standards Institute for alkaloids and derivatives against and genotypes VNI and VGI, respectively. A single active compound was further evaluated against . genotypes VNII, VNIII, and VNIV, . genotypes VGI, VGIII, and VGIV, ATCC 36232, for cytotoxicity against the MRC-5 lineage of human fibroblasts and for effects on fungal cells (cell wall, ergosterol, and leakage of nucleic acids).
RESULTS
Screening of 11 compounds revealed 8-nitroharmane as a significant inhibitor (MIC 40 g/mL) of several and genotypes. It was not toxic to fibroblasts (IC > 50 g/mL) nor did it alter fungal cell walls or the concentration of ergosterol in or . It increased leakage of substances that absorb at 260 nm.
CONCLUSIONS
The synthetic -carboline 8-nitroharmane significantly inhibits pathogenic species and is interesting as a lead compound towards new therapy for infections.
背景
隐球菌病是一种预后不良的真菌疾病，因其致病性以及用于治疗的药物的毒性。本研究的目的是调查咔唑和β-咔啉生物碱及其衍生物对新型隐球菌和格特隐球菌的药用潜力。
方法
根据临床和实验室标准协会的建议，分别确定生物碱及其衍生物对新型隐球菌基因型VNI和格特隐球菌基因型VGI的最低抑菌浓度（MIC）。进一步评估单一活性化合物对新型隐球菌基因型VNII、VNIII和VNIV、格特隐球菌基因型VGI、VGIII和VGIV、新型隐球菌ATCC 36232的细胞毒性，以及对人成纤维细胞MRC-5谱系的细胞毒性和对真菌细胞的影响（细胞壁、麦角甾醇和核酸泄漏）。
结果
对11种化合物的筛选显示，8-硝基哈尔满是几种新型隐球菌和格特隐球菌基因型的有效抑制剂（MIC为40μg/mL）。它对成纤维细胞无毒（IC>50μg/mL），也不会改变新型隐球菌或格特隐球菌的真菌细胞壁或麦角甾醇浓度。它增加了在260nm处有吸收的物质的泄漏。
结论
合成的β-咔啉8-硝基哈尔满能显著抑制致病性隐球菌属物种，作为一种用于隐球菌感染新疗法的先导化合物很有意义。
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