Mitschke Nico, Chemutai Sum Winnie, Hassan Khadija, Kirchenwitz Marco, Schrey Hedda, Gerhards Luca, Kellner Harald, Stradal Theresia E B, Matasyoh Josphat C, Stadler Marc
Department of Microbial Drugs, Helmholtz Centre for Infection Research GmbH Inhoffenstrasse 7 38124 Braunschweig Germany
Institute of Microbiology, Technische Universität Braunschweig Spielmannstraße 7 38106 Braunschweig Germany
RSC Adv. 2023 Aug 31;13(37):25752-25761. doi: 10.1039/d3ra04204a. eCollection 2023 Aug 29.
Four previously undescribed drimane sesquiterpenoids were isolated from submerged cultures of the wood-inhabiting basidiomycete along with two compounds that were previously reported as synthetic or biotransformation compounds but not as natural products. The constitution and relative configuration of these compounds was determined based on high-resolution electrospray ionization mass spectrometry as well as by 1D and 2D nuclear magnetic resonance spectroscopy. The absolute configurations were established based on exemplary calculation of circular dichroism spectra and comparison with measured data as well as on biogenetic considerations. The biological activities of the isolated compounds were assessed in antimicrobial, cytotoxicity and neurotrophic assays. 10-Methoxycarbonyl-10-norisodrimenin (3) exhibited weak activity against the Gram-positive bacterium and the zygomycete with minimal inhibitory concentrations of 66.7 μg mL. In addition, compound 3 showed weak inhibition of the mammalian cell line KB3.1 (human endocervical adenocarcinoma) with a half maximal inhibitory concentration of 21.2 μM. The neurotrophic activities of 15-hydroxyisodrimenin (1) and 10-carboxy-10-norisodrimenin (5) were assed in neurite outgrowth and real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays. When supplemented with 5 ng mL nerve growth factor (NGF), the drimanes 1 and 5 induced neurite outgrowth in PC-12 (rat pheochromocytoma) cells compared to cells solely treated with NGF. As evaluated by RT-qPCR, compounds 1 and 5 also increased NGF and brain-derived neurotrophic factor expression levels in 1321N1 astrocytoma cells. Interestingly, the current study only represents the second report on neurotrophic activities of this widespread class of terpenoids. The only other available study deals with , another basidiomycete that can produce drimanes and cyathanes, but is only distantly related to and the Hericiaceae.
从一种木生担子菌的深层培养物中分离出了四种此前未被描述的菖蒲烷倍半萜类化合物，同时还分离出了两种化合物，这两种化合物此前被报道为合成或生物转化产物，但并非天然产物。这些化合物的结构和相对构型通过高分辨率电喷雾电离质谱以及一维和二维核磁共振光谱得以确定。绝对构型基于圆二色光谱的示例计算、与实测数据的比较以及生源学考虑得以确定。对分离出的化合物的生物活性进行了抗菌、细胞毒性和神经营养活性测定。10 - 甲氧基羰基 - 10 - 去甲异菖蒲烯醇（3）对革兰氏阳性菌和接合菌表现出较弱的活性，最小抑菌浓度为66.7 μg/mL。此外，化合物3对哺乳动物细胞系KB3.1（人宫颈腺癌）表现出较弱的抑制作用，半最大抑制浓度为21.2 μM。在神经突生长和实时定量逆转录聚合酶链反应（RT - qPCR）测定中评估了15 - 羟基异菖蒲烯醇（1）和10 - 羧基 - 10 - 去甲异菖蒲烯醇（5）的神经营养活性。当补充5 ng/mL神经生长因子（NGF）时，与仅用NGF处理的细胞相比，菖蒲烷类化合物1和5在PC - 12（大鼠嗜铬细胞瘤）细胞中诱导了神经突生长。通过RT - qPCR评估，化合物1和5还增加了1321N1星形细胞瘤细胞中NGF和脑源性神经营养因子的表达水平。有趣的是，当前的研究只是关于这类广泛存在的萜类化合物神经营养活性的第二篇报道。另一项可用的研究涉及另一种担子菌，它也能产生菖蒲烷类化合物和杯伞烷类化合物，但与该菌以及刺革菌科的亲缘关系较远。
