Institute for Medical Research and Occupational Health, Ksaverska Cesta 2, 10000 Zagreb, Croatia.
Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 19, 10000 Zagreb, Croatia.
Molecules. 2020 Oct 22;25(21):4872. doi: 10.3390/molecules25214872.
A library of amine, oxime, ether, epoxy and acyl derivatives of the benzobicyclo[3.2.1]octene were synthesized and evaluated as inhibitors of both human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The majority of the tested compounds exhibited higher selectivity for BChE. Structural adjustment for AChE seems to have been achieved by acylation, and the furan ring opening of furo-benzobicyclo[3.2.1]octadiene results for compound with the highest AChE affinity (IC = 8.3 µM). Interestingly, its analogue, an oxime ether with a benzobicyclo[3.2.1]-skeleton, compound was one of the most potent BChE inhibitors in this study (IC = 31 µM), but not as potent as , an ether derivative of the benzobicyclo[3.2.1]octene with an additional phenyl substituent (IC = 17 µM). Therefore, we identified several cholinesterase inhibitors with a potential for further development as potential drugs for the treatment of neurodegenerative diseases.
合成了一系列苯并双环[3.2.1]辛烯的胺、肟、醚、环氧化物和酰基衍生物，并评估了它们对人乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）的抑制作用。大多数测试化合物对 BChE 表现出更高的选择性。似乎通过酰化实现了对 AChE 的结构调整，而呋喃环开环则导致呋喃苯并双环[3.2.1]辛二烯化合物 具有最高的 AChE 亲和力（IC = 8.3 µM）。有趣的是，其类似物，即具有苯并双环[3.2.1]骨架的肟醚化合物 ，是本研究中最有效的 BChE 抑制剂之一（IC = 31 µM），但其效力不及苯并双环[3.2.1]辛烯的醚衍生物 ，后者具有额外的苯基取代基（IC = 17 µM）。因此，我们确定了几种具有进一步开发潜力的胆碱酯酶抑制剂，作为治疗神经退行性疾病的潜在药物。
