Fayez Shaimaa, Bruhn Torsten, Feineis Doris, Assi Laurent Aké, Kushwaha Prem Prakash, Kumar Shashank, Bringmann Gerhard
Institute of Organic Chemistry, University of Würzburg Am Hubland D-97074 Würzburg Germany
Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Organization of African Unity Street 1 11566 Cairo Egypt.
RSC Adv. 2022 Oct 12;12(45):28916-28928. doi: 10.1039/d2ra05758a. eCollection 2022 Oct 11.
The West African liana is a rich source of structurally most diverse naphthylisoquinoline alkaloids. From its roots, a series of four novel representatives, named ancistrobrevolines A-D (14-17) have now been isolated, displaying an unprecedented heterocyclic ring system, where the usual isoquinoline entity is replaced by a ring-contracted isoindolinone part. Their constitutions were elucidated by 1D and 2D NMR and HR-ESI-MS. The absolute configurations at the chiral axis and at the stereogenic center were assigned by using experimental and computational electronic circular dichroism (ECD) investigations and a ruthenium-mediated oxidative degradation, respectively. For the biosynthetic origin of the isoindolinones from 'normal' naphthyltetrahydroisoquinolines, a hypothetic pathway is presented. It involves oxidative decarboxylation steps leading to a ring contraction by a benzilic acid rearrangement. Ancistrobrevolines A (14) and B (15) were found to display moderate cytotoxic effects (up to 72%) against MCF-7 breast and A549 lung cancer cells and to reduce the formation of spheroids (mammospheres) in the breast cancer cell line.
西非藤本植物是结构最为多样的萘基异喹啉生物碱的丰富来源。从其根部现已分离出一系列四种新型化合物，命名为钩藤短碱A - D（14 - 17），它们展示出前所未有的杂环系统，其中常见的异喹啉部分被一个环收缩的异吲哚啉酮部分所取代。通过一维和二维核磁共振以及高分辨电喷雾电离质谱对它们的结构进行了阐明。分别利用实验和计算电子圆二色光谱（ECD）研究以及钌介导的氧化降解确定了手性轴和立体中心的绝对构型。对于从“正常”萘基四氢异喹啉生成异吲哚啉酮的生物合成起源，提出了一条假设途径。它涉及氧化脱羧步骤，通过二苯乙醇酸重排导致环收缩。发现钩藤短碱A（14）和B（15）对MCF - 7乳腺癌细胞和A549肺癌细胞显示出中等程度的细胞毒性作用（高达72%），并减少乳腺癌细胞系中球体（乳腺球）的形成。
