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交替镰孢内生真菌对麻疯树的代谢组学分析及体外和体内抗菌和抗癌活性评估。

Metabolite profiling, in vitro and in silico assessment of antibacterial and anticancer activities of Alternaria alternata endophytic in Jatropha heynei.

机构信息

Department of P.G. Studies and Research in Applied Botany, School of Biosciences, Kuvempu University, Jnana Sahyadri, Shankaraghatta, 577451, Shivamogga, India.

出版信息

Arch Microbiol. 2023 Jan 10;205(2):61. doi: 10.1007/s00203-022-03388-6.

DOI:10.1007/s00203-022-03388-6
PMID:36625985
Abstract

Fungal endophytes produce a range of structurally diverse metabolites with bioactive principles. In this study, an endophytic fungus Alternaria alternata was isolated from Jatropha heynei and cultured in potato dextrose liquid broth. Culture filtrate of A. alternata was extracted in ethyl acetate and metabolites were characterized by QTOF-HRLCMS. Among compounds detected, spectral compounds such as kigelinone, and levofuraltadone were reported with antibacterial property, while 2-hydroxychrasophanol, isoathyriol, glycophymoline, columbianetin and kaempferol 3-O-β-D- galactoside were reported with cytotoxic properties. Partially purified metabolites of A. alternata showed significant antibacterial activity against tested clinical bacterial strains by agar well diffusion method. High zone of inhibition was recorded against Enterococcus faecalis, Pseudomonas syringae and Klebsiella pneumoniae. In vitro anticancer activity of fungal extract by MTT assay displayed high cytotoxic effect on human lung carcinoma cancer cell line (A549) with IC value of 393.52 µg ml, and without any significant cytotoxic effect on human breast cancer cell line (MCF-7). Further, antibacterial and anticancer spectral compounds of A. alternata were subjected to molecular docking analysis with antibacterial target proteins such as tellurite resistance protein (2JXU), indole-3-acetaldehyde dehydrogenase (5IUU) and alkyl hydroperoxide reductase (5Y63), and anticancer target human apoptotic regulator protein (1G5M). The results of the study indicated that kigelinone, levofuraltadone, 2-hydroxychrasophanol and isoathyriol in the fungal extract have significant binding modes, with best binding energy scores with their respective antibacterial and anticancer target proteins. Alternaria alternata resident in J. heynei offers a promising source of broad-spectrum antibacterial and anticancer compounds.

摘要

真菌内生菌产生具有生物活性的结构多样的代谢产物。在这项研究中,从麻疯树中分离出一株链格孢属真菌,并在土豆葡萄糖液体培养液中培养。用乙酸乙酯提取链格孢属真菌的培养液滤液,并用 QTOF-HRLCMS 对代谢产物进行了表征。在所检测到的化合物中,谱化合物如 kigelinone 和 levofuraltadone 具有抗菌活性,而 2-羟基 chrasophanol、isoathyriol、glycophymoline、columbianetin 和 kaempferol 3-O-β-D-半乳糖苷具有细胞毒性。通过琼脂孔扩散法,部分纯化的链格孢属代谢产物对测试的临床细菌菌株表现出显著的抗菌活性。对粪肠球菌、丁香假单胞菌和肺炎克雷伯菌的抑菌圈较大。MTT 法测定真菌提取物的体外抗癌活性,对人肺癌癌细胞系(A549)表现出高细胞毒性,IC 值为 393.52μg/ml,对人乳腺癌细胞系(MCF-7)无明显细胞毒性。此外,对链格孢属的抗菌和抗癌谱化合物进行了分子对接分析,对接物为抗菌靶蛋白,如碲酸盐抗性蛋白(2JXU)、吲哚-3-乙醛脱氢酶(5IUU)和烷基过氧化物还原酶(5Y63),以及抗癌靶蛋白人凋亡调节蛋白(1G5M)。研究结果表明,真菌提取物中的 kigelinone、levofuraltadone、2-羟基 chrasophanol 和 isoathyriol 与各自的抗菌和抗癌靶蛋白具有显著的结合模式,具有最佳的结合能评分。驻留在麻疯树中的链格孢属真菌提供了一种有前途的广谱抗菌和抗癌化合物的来源。

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