Petrova Anastasiya V, Kazakova Oxana B, Nazarov Ivan S, Csuk René, Heise Niels V
Ufa Institute of Chemistry of the Ufa Federal Research Center of the, Russian Academy of Sciences, 71, prospect Octyabrya, Ufa, 450054, Russian Federation.
Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120, Halle (Saale), Germany.
Chem Biodivers. 2023 Apr;20(4):e202300185. doi: 10.1002/cbdv.202300185. Epub 2023 Mar 31.
A series of new lupane, ursane, and oleanane type triterpenic A-seco-derivatives containing bromo-, azido-, alkyne-, 1H-tetrazol-5-yl-, 5-methyloxazol-2-yl-, N-(4-(4-methylpiperazin-1-yl)but-2-yn-1-yl), and a carbonyl group at C2, C24, C28, C30 positions has been synthesized. The bioactivity was evaluated by Ellman's method, and the results showed that most of the compounds displayed moderate acetylcholinesterase inhibitory activities in vitro. Among them, A-seco-derivatives of 28-oxo-allobetuline and betulinic acid with bromo- and azido-groups exhibited the most potent inhibitory activity against AChE. Extra experiments showed methyl 2-cyano-3,4-seco-dibromo- and 2-cyano-3,4-seco-diazido-derivatives of betulinic acid as mixed-type inhibitors, with Ki values as low as K =0.18 μM and K =0.21 μM, respectively.
已合成了一系列新的羽扇豆烷型、乌苏烷型和齐墩果烷型三萜A-裂环衍生物，这些衍生物在C2、C24、C28、C30位含有溴基、叠氮基、炔基、1H-四唑-5-基、5-甲基恶唑-2-基、N-(4-(4-甲基哌嗪-1-基)丁-2-炔-1-基)以及一个羰基。通过埃尔曼法评估了其生物活性，结果表明大多数化合物在体外表现出中等程度的乙酰胆碱酯酶抑制活性。其中，具有溴基和叠氮基的28-氧代别白桦脂醇和桦木酸的A-裂环衍生物对乙酰胆碱酯酶表现出最强的抑制活性。额外实验表明，桦木酸的2-氰基-3,4-裂环二溴代和2-氰基-3,4-裂环二叠氮基衍生物为混合型抑制剂，其抑制常数Ki值分别低至K =0.18 μM和K =0.21 μM。
