2致分化PC12细胞损伤的保护作用> 川芎嗪中间体的合成及其对CoCl2致分化PC12细胞损(4)
2. School of Preclinical Medicine， Beijing University of Chinese Medicine， Beijing 100029， China)
[Abstract] Ligustrazine， one of the major effective components of the Chinese traditional medicinal herb Ligusticum Chuanxiong Hort， has been reported plenty of biological activities， such as protect cardiovascular and cerebrovascular， neuroprotection and anti-tumor， et al. Because of its remarkable effects， studies on structural modification of ligustrazine have attracted much attention. Ligustrazine synthetic derivatives reported in recent decades are mainly derived from four primary intermediates (TMP-COOH， TMP-OH， TMP-NH2， HO-TMP-OH). To explore the neuroprotection activitiy of ligustrazine intermediates， six ligustrazine intermediates (2， 5， 8， 11， 12， 13) were synthesized and their protective effects against CoCl2-induced neurotoxicity in differentiated PC12 cells were studied. The target compounds were prepared via different chemical methods， including oxidation， substitution， esterification and amidation without changing the structure nucleus of ligustrazine. Compared with TMP (EC50=56.03 μmol·L-1)， four compounds (2， 5， 12 and 13) exhibited higher activity (EC50 < 50 μmol·L-1) respectively， of which， compound 2 displayed the highest protective effect against the damaged PC12 cells (EC50=32.86 μmol·L-1)， but target compounds 8 and 11 appeared lower activity (EC50 > 70 μmol·L-1). By structure-activity relationships analysis， the introduction of carboxyl， amino to the side chain of ligustrazine and appropriately increase the proportion of ligustrazine may contribute to enhance its neuroprotective activity， which provides a reference for the design， synthesis and activity screening of relevant series of ligustrazine derivatives in the future.
[Key words] ligustrazine intermediates； PC12 cell； neuroprotection； structure-activity relationships, 百拇医药(李国梁 王鹏龙 徐昕 林锦璇 褚福浩 宋霁翔 周燊 王咪娜 张宇忠 雷海民)
[Abstract] Ligustrazine， one of the major effective components of the Chinese traditional medicinal herb Ligusticum Chuanxiong Hort， has been reported plenty of biological activities， such as protect cardiovascular and cerebrovascular， neuroprotection and anti-tumor， et al. Because of its remarkable effects， studies on structural modification of ligustrazine have attracted much attention. Ligustrazine synthetic derivatives reported in recent decades are mainly derived from four primary intermediates (TMP-COOH， TMP-OH， TMP-NH2， HO-TMP-OH). To explore the neuroprotection activitiy of ligustrazine intermediates， six ligustrazine intermediates (2， 5， 8， 11， 12， 13) were synthesized and their protective effects against CoCl2-induced neurotoxicity in differentiated PC12 cells were studied. The target compounds were prepared via different chemical methods， including oxidation， substitution， esterification and amidation without changing the structure nucleus of ligustrazine. Compared with TMP (EC50=56.03 μmol·L-1)， four compounds (2， 5， 12 and 13) exhibited higher activity (EC50 < 50 μmol·L-1) respectively， of which， compound 2 displayed the highest protective effect against the damaged PC12 cells (EC50=32.86 μmol·L-1)， but target compounds 8 and 11 appeared lower activity (EC50 > 70 μmol·L-1). By structure-activity relationships analysis， the introduction of carboxyl， amino to the side chain of ligustrazine and appropriately increase the proportion of ligustrazine may contribute to enhance its neuroprotective activity， which provides a reference for the design， synthesis and activity screening of relevant series of ligustrazine derivatives in the future.
[Key words] ligustrazine intermediates； PC12 cell； neuroprotection； structure-activity relationships, 百拇医药(李国梁 王鹏龙 徐昕 林锦璇 褚福浩 宋霁翔 周燊 王咪娜 张宇忠 雷海民)