Bioorganic Chemistry ( IF 5.1 ) Pub Date : 2018-03-03 , DOI: 10.1016/j.bioorg.2018.03.003 Marek Bajda , Kamil Łątka , Michalina Hebda , Jakub Jończyk , Barbara Malawska
Selective butyrylcholinesterase inhibitors could be the promising drug candidates, used in treatment of Alzheimer's disease. The study describes the synthesis and biological activity of novel carbamate derivatives with N-phenylpiperazine, N-benzylpiperazine and 4-benzylpiperidine moieties. Biological studies revealed that most of these compounds displayed significant activity against BuChE. Compound 16 (3-(4-phenyl-piperazin-1-ylmethyl)-phenyl phenylcarbamate) turned out to be the most active (IC50 = 2.00 μM for BuChE). For all synthesized compounds lipophilicity and other physicochemical properties were calculated using computer programs. Relationship between these properties and activity was also checked. Binding mode with enzyme and the ensuing differences in activity were explained by the molecular modeling studies.
中文翻译:
新型氨基甲酸酯衍生物作为选择性丁酰胆碱酯酶抑制剂
选择性丁酰胆碱酯酶抑制剂可能是用于治疗阿尔茨海默氏病的有前途的候选药物。该研究描述了具有N-苯基哌嗪,N-苄基哌嗪和4-苄基哌啶部分的新型氨基甲酸酯衍生物的合成和生物活性。生物学研究表明,这些化合物大多数显示出对BuChE的显着活性。化合物16(3-(4-苯基-哌嗪-1-基甲基)-苯基苯基氨基甲酸酯)活性最高(IC 50 对于BuChE = 2.00μM)。对于所有合成的化合物,使用计算机程序计算亲脂性和其他理化性质。还检查了这些性质和活性之间的关系。分子模型研究解释了与酶的结合方式以及随之而来的活性差异。