Stępnik Katarzyna, Kukula-Koch Wirginia, Płaziński Wojciech
Department of Physical Chemistry, Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie-Sklodowska University in Lublin, Pl. M. Curie-Skłodowskiej 3, 20-031 Lublin, Poland.
Department of Pharmacognosy with Medicinal Plants Garden, Medical University of Lublin, ul. Chodźki 1, 20-093 Lublin, Poland.
Biomolecules. 2023 Sep 6;13(9):1357. doi: 10.3390/biom13091357.
The acetylcholinesterase-inhibitory potential of the oleanane-type triterpenes and their glycosides from thebark of (Combreatceae), i.e.,arjunic acid, arjunolic acid, arjungenin, arjunglucoside I, sericic acid and arjunetin, is presented. The studies are based on in silico pharmacokinetic and biomimetic studies, acetylcholinesterase (AChE)-inhibitory activity tests and molecular-docking research. Based on the calculated pharmacokinetic parameters, arjunetin and arjunglucoside I are indicated as able to cross the blood-brain barrier. The compounds of interest exhibit a marked acetylcholinesterase inhibitory potential, which was tested in the TLC bioautography test. The longest time to reach brain equilibrium is observed for both the arjunic and arjunolic acids and the shortest one for arjunetin. All of the compounds exhibit a high and relatively similar magnitude of binding energies, varying from ca. -15 to -13 kcal/mol. The superposition of the most favorable positions of all ligands interacting with AChE is analyzed. The correlation between the experimentally determined IC values and the steric parameters of the molecules is investigated. The inhibition of the enzyme by the analyzed compounds shows their potential to be used as cognition-enhancing agents. For the most potent compound (arjunglucoside I; ARG), the kinetics of AChE inhibition were tested. The Michaelis-Menten constant (Km) for the hydrolysis of the acetylthiocholine iodide substrate was calculated to be 0.011 mM.
介绍了使君子科植物树皮中齐墩果烷型三萜及其糖苷（即阿朱那酸、阿朱诺酸、阿朱诺配基、阿朱诺糖苷I、丝氨酸和阿朱那亭）的乙酰胆碱酯酶抑制潜力。这些研究基于计算机模拟药代动力学和仿生学研究、乙酰胆碱酯酶（AChE）抑制活性测试以及分子对接研究。根据计算出的药代动力学参数，阿朱那亭和阿朱诺糖苷I被表明能够穿过血脑屏障。所关注的化合物表现出显著的乙酰胆碱酯酶抑制潜力，这在薄层色谱生物自显影试验中得到了测试。阿朱那酸和阿朱诺酸达到脑平衡的时间最长，而阿朱那亭的时间最短。所有化合物都表现出较高且相对相似的结合能，范围约为 -15至 -13千卡/摩尔。分析了所有与AChE相互作用的配体最有利位置的叠加情况。研究了实验测定的IC值与分子空间参数之间的相关性。所分析化合物对该酶的抑制作用表明它们有潜力用作认知增强剂。对于最有效的化合物（阿朱诺糖苷I；ARG），测试了其对AChE抑制的动力学。计算得出碘化硫代乙酰胆碱底物水解的米氏常数（Km）为0.011 mM。
