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.
Institute of Organic Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany.
Bioorg Med Chem. 2021 Jan 15;30:115950. doi: 10.1016/j.bmc.2020.115950. Epub 2020 Dec 15.
From the leaves of Ancistrocladus abbreviatus (Ancistrocladaceae), six 5,1'-coupled naphthyldihydroisoquinoline alkaloids were isolated, ancistrobrevidines A-C (5-7), 5-epi-dioncophyllidine C (10), 6-O-methylhamatinine (8), and 6-O-methylancistectorine A (9); the two latter compounds were already known from related plants. Most strikingly, this series comprises alkaloids belonging to three different subclasses of naphthylisoquinolines. Ancistrobrevidine C (7) and the alkaloids 8 and 9, displaying the S-configuration at C-3 and an oxygen function at C-6, are three further representatives of the large subgroup of 5,1'-coupled Ancistrocladaceae-type compounds found in nature. 5-epi-Dioncophyllidine C (10), lacking an oxygen function at C-6 and having the R-configuration at C-3, is only the third representative of a 5,1'-linked Dioncophyllaceae-type naphthylisoquinoline. Likewise rare are 5,1'-coupled hybrid-type alkaloids, which are 6-oxygenated and 3R-configured. The ancistrobrevidines A (5) and B (6) are the only second and third examples of such 5,1'-linked naphthylisoquinolines in Ancistrocladus species showing the landmarks of both, Ancistrocladaceae- and Dioncophyllaceae-type naphthylisoquinolines. In the roots of A. abbreviatus, two further unprecedented 5,1'-coupled alkaloids were discovered, ancistrobreviquinones A (11) and B (12), consisting of a 3,4-naphthoquinone portion coupled to a tetrahydroisoquinoline subunit. They are the very first quinoid naphthylisoquinolines possessing an ortho-diketone entity. Ancistrobrevidine C (7) exerted pronounced antiproliferative activities against HeLa cervical cancer cells and preferential cytotoxicity towards PANC-1 human pancreatic cancer cells under nutrient-deprived conditions following the antiausterity approach. Moreover, 7 suppressed the migration of PANC-1 cells and significantly inhibited colony formation under nutrient-rich conditions in a concentration-dependent manner, and induced dramatic alteration in cell morphology, leading to cell death.
从短梗南五味子 (Ancistrocladaceae) 的叶子中分离得到了 6 种 5,1'-偶联的萘基二氢异喹啉生物碱，分别为 ancistrobrevidines A-C (5-7)、5-epi-dioncophyllidine C (10)、6-O-甲基汉亭碱 (8) 和 6-O-甲基 ancistectorine A (9)；后两种化合物已在相关植物中被发现。最引人注目的是，这一系列包含属于三种不同萘基异喹啉亚类的生物碱。Ancistrobrevidine C (7) 以及生物碱 8 和 9，在 C-3 位具有 S 构型和 C-6 位的氧功能，是在自然界中发现的具有大的 5,1'-偶联 Ancistrocladaceae 型化合物亚组的另外三种代表。5-epi-Dioncophyllidine C (10) 缺乏 C-6 位的氧功能，在 C-3 位具有 R 构型，是 Dioncophyllaceae 型萘基异喹啉的第 3 个代表。同样罕见的是 5,1'-偶联的杂种型生物碱，它们是 6-氧化和 3R 构型的。Ancistrobrevidines A (5) 和 B (6) 是 Ancistrocladus 属中仅有的第二个和第三个具有这种 5,1'-连接的萘基异喹啉的例子，它们显示了 Ancistrocladaceae 型和 Dioncophyllaceae 型萘基异喹啉的标志。在短梗南五味子的根中，还发现了另外两种前所未有的 5,1'-偶联生物碱，ancistrobreviquinones A (11) 和 B (12)，它们由一个 3,4-萘醌部分与一个四氢异喹啉亚基偶联而成。它们是具有邻二酮实体的第一个醌型萘基异喹啉。Ancistrobrevidine C (7) 在营养剥夺条件下，通过抗萎缩方法，对 HeLa 宫颈癌细胞表现出明显的抗增殖活性和对 PANC-1 人胰腺癌细胞的选择性细胞毒性。此外，7 以浓度依赖的方式抑制富含营养条件下 PANC-1 细胞的迁移和集落形成，并显著诱导细胞形态的剧烈改变，导致细胞死亡。
