Subko Karolina, Kildgaard Sara, Vicente Francisca, Reyes Fernando, Genilloud Olga, Larsen Thomas O
DTU Bioengineering, Technical University of Denmark, Søltofts Plads 221, DK-2800 Kgs. Lyngby, Denmark.
Department of Biology, Universitetsparken 15, DK-2100 København Ø, Denmark.
Mar Drugs. 2021 Jan 20;19(2):46. doi: 10.3390/md19020046.
The marine-derived fungus is a chemically talented fungus producing several classes of bioactive metabolites, including meroterpenoids of the ascochlorin family. The targeted dereplication of fungal extracts by UHPLC-DAD-QTOF-MS revealed the presence of several new along with multiple known ascochlorin analogues (-). Their structures and relative configuration were characterized by 1D and 2D NMR. Further targeted dereplication based on a novel 1,4-benzoquinone sesquiterpene derivative, fimetarin A (), resulted in the identification of three additional fimetarin analogues, fimetarins B-D (-), with their tentative structures proposed from detailed MS/HRMS analysis. In total, four new and eight known ascochlorin/fimetarin analogues were tested for their antimicrobial activity, identifying the analogues with a 5-chloroorcylaldehyde moiety to be more active than the benzoquinone analogue. Additionally, the presence of two conjugated double bonds at C-2'/C-3' and C-4'/C-5' were found to be essential for the observed antifungal activity, whereas the single, untailored bonds at C-4'/C-5' and C-8'/C-9' were suggested to be necessary for the observed antibacterial activity.
海洋来源真菌是一种具有化学天赋的真菌，能产生几类生物活性代谢产物，包括阿斯科氯素家族的半萜类化合物。通过超高效液相色谱-二极管阵列-四极杆飞行时间质谱对真菌提取物进行靶向去重复分析，发现了几种新的以及多种已知的阿斯科氯素类似物（-）。它们的结构和相对构型通过一维和二维核磁共振进行了表征。基于一种新型的1,4-苯醌倍半萜衍生物菲美他林A（）进行进一步的靶向去重复分析，结果鉴定出另外三种菲美他林类似物，即菲美他林B-D（-），并通过详细的质谱/高分辨质谱分析推测出了它们的暂定结构。总共对四种新的和八种已知的阿斯科氯素/菲美他林类似物进行了抗菌活性测试，发现具有5-氯奥氯醛部分的类似物比苯醌类似物更具活性。此外，发现C-2'/C-3'和C-4'/C-5'处的两个共轭双键对于观察到的抗真菌活性至关重要，而C-4'/C-5'和C-8'/C-9'处的单键、未修饰的键对于观察到的抗菌活性被认为是必要的。
