Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, People's Republic of China.
Bioorg Chem. 2021 May;110:104826. doi: 10.1016/j.bioorg.2021.104826. Epub 2021 Mar 17.
Coculturing two or more fungi is a useful strategy to awaken the silent genes to produce structurally diverse and bioactive natural products. Through the coculture of Pestalotiopsis sp. and Penicillium bialowiezense, six new isoprenylated chromane derivatives, including two pairs of enantiomeric ones (1a/1b-2a/2b) and two optical pure ones (3-4), two new isoprenylated phenol glucoside derivatives (6-7), as well as eight known structural analogues (5 and 8-14), were obtained. The structures of these new compounds were characterized by NMR spectroscopy, single-crystal X-ray crystallography, and ECD calculation. The Δ double bond of pestaloficin D (5) was revised to E-configurated based on the extensive spectroscopic analyses. Compounds 1a/1b and 2a/2b were the first examples of enantiomeric isoprenylated chromane derivatives, which were successfully separated by chiral HPLC. Additionally, all the isolated compounds were evaluated for the in vitro β-glucuronidase (GUS) and butyrylcholinesterase (BChE) inhibitory activities. Compounds 1a and 1b showed significant β-glucuronidase inhibitory potency with IC values of 7.6 and 10.3 μM, respectively. Compound 14 exhibited moderate BChE inhibitory activity with an IC value of 21.3 μM. In addition, the structure-enzyme inhibitory activity relationship of compounds 1-14 is discussed.
共培养两种或更多真菌是一种有用的策略，可以唤醒沉默基因，产生结构多样和具有生物活性的天然产物。通过 Pestalotiopsis sp. 和 Penicillium bialowiezense 的共培养，获得了六个新的异戊烯基色烷衍生物，包括两对对映异构体（1a/1b-2a/2b）和两个光学纯化合物（3-4），两个新的异戊烯基苯酚葡萄糖苷衍生物（6-7），以及八个已知的结构类似物（5 和 8-14）。这些新化合物的结构通过 NMR 光谱、单晶 X 射线晶体学和 ECD 计算进行了表征。根据广泛的光谱分析，修订了 pestaloficin D（5）的Δ双键为 E 构型。1a/1b 和 2a/2b 是对映异构异戊烯基色烷衍生物的第一个例子，它们通过手性 HPLC 成功分离。此外，所有分离得到的化合物都进行了体外β-葡萄糖醛酸酶（GUS）和丁酰胆碱酯酶（BChE）抑制活性评估。化合物 1a 和 1b 对β-葡萄糖醛酸酶具有显著的抑制活性，IC 值分别为 7.6 和 10.3 μM。化合物 14 对丁酰胆碱酯酶具有中等抑制活性，IC 值为 21.3 μM。此外，还讨论了化合物 1-14 的结构-酶抑制活性关系。
