Shaaban Mohamed, Nasr Hamdi, Mohamed Tahia K, Mahmoud Samy F, El-Metwally Mohammad M, Abdelwahab Ahmed B
Chemistry of Natural Compounds Department, Pharmaceutical Industries Research Institute, National Research Centre, El-Behoos St. 33, Dokki, Cairo 12622, Egypt.
Institute of Organic and Biomolecular Chemistry, University of Göttingen, Tammannstraße 2, D-37077 Göttingen, Germany.
Z Naturforsch C J Biosci. 2022 Mar 18;78(3-4):149-156. doi: 10.1515/znc-2021-0284. Print 2023 Mar 28.
Four bioactive metabolites; ergosterol (), peroxy ergosterol (), -cyclopiazonic acid () and kojic acid (), were isolated from the fungal sp. MM21. Their structures were assigned by cumulative analysis of NMR and mass spectra, and comparison with literature. The antimicrobial activity of the fungus supernatant, mycelial cake, cumulative crude extract and compounds was broadly studied against 11 diverse pathogens, revealing auspicious activity results. Based on the molecular docking, ergosterol () and peroxy ergosterol () were picked up to be computationally tested against topoisomerase IV of The nominated enzyme is a possible target for the antibacterial activity of triterpenoidal/steroidal compounds. Compounds showed a deep inserting inside the enzyme groove recording a good binding affinity of -8.1 and -8.4 kcal/mol, respectively. Noteworthy that the antibacterial activity of ergosterol was higher (14-17 mm) than peroxy ergosterol (11-14 mm), although ergosterol formed only one hydrogen bond with the target, while peroxy ergosterol formed three hydrogen bonds. Such higher antibacterial activity of ergosterol may be attributed to its interference with other proteins included in this inhibition. The cytotoxic activity was tested against brine shrimp, revealing 100% mortality for the supernatant, crude extract and whole isolated compounds. Such strong cytotoxicity is attributed most likely to the abundant productivity/concentration of -cyclopiazonic acid and kojic acid.
从真菌菌株MM21中分离出四种生物活性代谢物：麦角固醇（）、过氧麦角固醇（）、β-环匹阿尼酸（）和曲酸（）。通过核磁共振和质谱的累积分析并与文献进行比较确定了它们的结构。广泛研究了该真菌的上清液、菌丝饼、累积粗提物及化合物对11种不同病原体的抗菌活性，结果显示出良好的活性。基于分子对接，挑选出麦角固醇（）和过氧麦角固醇（）针对金黄色葡萄球菌的拓扑异构酶IV进行计算测试。指定的该酶是三萜类/甾体类化合物抗菌活性的一个可能靶点。化合物分别显示出深入插入酶凹槽内，结合亲和力良好，分别为-8.1和-8.4千卡/摩尔。值得注意的是，麦角固醇的抗菌活性（14 - 17毫米）高于过氧麦角固醇（11 - 14毫米），尽管麦角固醇仅与靶点形成一个氢键，而过氧麦角固醇形成三个氢键。麦角固醇这种较高的抗菌活性可能归因于其对该抑制作用中包含的其他蛋白质的干扰。针对卤虫测试了细胞毒性，结果显示上清液、粗提物及所有分离出的化合物的死亡率均为100%。这种强细胞毒性最有可能归因于β-环匹阿尼酸和曲酸的大量产生/高浓度。
