State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510632, PR China; Center for Bioactive Natural Molecules and Innovative Drugs Research, and Guangdong Provincial Engineering Research Center for Modernization of TCM, College of Pharmacy, Jinan University, Guangzhou 510632, PR China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM & New Drugs Research, Jinan University, Guangzhou 510632, PR China; NMPA Key Laboratory for Quality Evaluation of TCM, Jinan University, Guangzhou 510632, PR China.
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510632, PR China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM & New Drugs Research, Jinan University, Guangzhou 510632, PR China.
Bioorg Chem. 2024 Oct;151:107664. doi: 10.1016/j.bioorg.2024.107664. Epub 2024 Jul 20.
Eleven undescribed monoterpenoid bisindole alkaloids, alstomaphyines A-K (1-11), along with three known analogues were isolated from the leaves and stem bark of the Alstonia macrophylla. Compounds 1-3 were unprecedented dimerization alkaloids incorporating a macroline-type motif with an ajmaline-type motif via a C-C linkage. Their structures and absolute configurations were elucidated by extensive spectroscopic analysis, electronic circular dichroism (ECD) calculation, and CD exciton chirality method. Compounds 1-3 displayed potential inhibitory bioactivity against AChE with IC values of 4.44 ± 0.35, 3.59 ± 0.18, and 3.71 ± 0.23 μM, respectively. Enzyme kinetic study revealed compounds 1-3 as mixed competitive AChE inhibitors. Besides, compounds 8 and 12-14 exhibited better cytotoxicity against human cancer cell line HT-29 than cisplatin. Flow cytometry data revealed that compounds 8, 13, and 14 significantly induced the HT-29 cells arrest in G0/G1 phase in a concentration-dependent manner.
从大驳骨（Alstonia macrophylla）的叶和茎皮中分离得到 11 种未被描述的单萜双吲哚生物碱，即 alstomaphyines A-K（1-11），以及 3 种已知类似物。化合物 1-3 是前所未有的二聚化生物碱，通过 C-C 键连接，将大环碱型结构与阿马林型结构结合在一起。通过广泛的光谱分析、电子圆二色性（ECD）计算和 CD 激子手性方法阐明了它们的结构和绝对构型。化合物 1-3 对 AChE 显示出潜在的抑制生物活性，IC 值分别为 4.44 ± 0.35、3.59 ± 0.18 和 3.71 ± 0.23 μM。酶动力学研究表明，化合物 1-3 是混合竞争型 AChE 抑制剂。此外，化合物 8 和 12-14 对人结肠癌细胞系 HT-29 的细胞毒性优于顺铂。流式细胞术数据显示，化合物 8、13 和 14 以浓度依赖性方式显著诱导 HT-29 细胞停滞在 G0/G1 期。
