石杉碱甲-E2020拼合物的合成及药理研究

合成了石杉碱甲-E2020的拼合物(1),并测定了1和中间产物10和11抑制乙酰胆碱酯酶的生物活性,它们的活性均低于E2020。对E2020和其中活性最高的10的8个异构体分别进行了构象分析及与TcAChE分子对接研究,结果表明,10的各异构体中只有RRZ型与AChE的结合能比E2020高,其它异构体的结合能均远小于E2020,这可能是10的活性比E2020低的原因。对异构体RRZ还进行了与TcAChE作用方式的研究,对接结果和结合能都说明10的RRZ型异构体的活性可能比E2020高。

Synthesis and pharmacological study of huperzine A-E2020 combined compound

The synthesis of huperzine - E2020 combined compound (1) has been accomplished and the activities of 1 and the intermediates 10 and 11 to inhibit the activity of acetylcholinesterase have been measured. Conformational analyses and molecular docking studies of E2020 and the eight isomers of 10 were carried out. The results indicated that binding energies of all isomers of 10 with TcAChE is much lower than E2020 except for RRZ, which might be the reason that the activity of 10 is lower than that of E2020. Interaction pattern of RRZ in TcAChE was also studied. Both docking studies and binding energy showed that the biological activity of RRZ might be higher than that of E2020.