Tang Luhong, Xiang Hong, Sun Yang, Qiu Liying, Chen Dongqun, Deng Chao, Chen Wei
School of Medicine and Pharmaceutics, Jiangnan University, 1800 Lihu Avenue, Wuxi JS 214122, People's Republic of China.
Appl Biochem Biotechnol. 2009 Aug;158(2):408-15. doi: 10.1007/s12010-008-8440-8. Epub 2008 Dec 13.
The monopalmityloxy shikimic acids have been synthesized from shikimic acid and palmitic acid catalyzed by Novozym 435 in 2-methyl-2-butanol. The anticoagulation activity in vivo via oral administration of monopalmityloxy shikimic acid has been evaluated through arteriovenous shunt model of rats and through the determination of thrombin time, prothrombin time, and activated partial thromboplastin time via rats. After reaction, the solid shikimic acid has been observed to dissolve in the reaction system completely. The subsequent high-performance liquid chromatography-mass spectroscopy analysis showed that the monopalmityloxy shikimic acids, as the only products, had been formed and the overall conversion rate was over 70%. The result showed that it had anti-thrombosis activity, could prolong the coagulating time and bleeding time in vivo, and lengthen the coagulating time in vitro. Compared with control group, the differences of the treatment group and aspirin group of rats are significant (P < 0.05) for prothrombin time and thrombin time, and very significant (P < 0.01) for activated partial thromboplastin time. It suggested that the product had the anticoagulation activity. The mechanism might be the co-action of the inhibition of intrinsic coagulation and the inhibition of extrinsic coagulation, and the inhibiting effect on intrinsic pathway is stronger than that on extrinsic pathway.
在2-甲基-2-丁醇中，以诺维信435为催化剂，由莽草酸和棕榈酸合成了单棕榈酰氧基莽草酸。通过大鼠动静脉分流模型，并通过测定大鼠的凝血酶时间、凝血酶原时间和活化部分凝血活酶时间，评估了口服单棕榈酰氧基莽草酸后的体内抗凝活性。反应后，观察到固体莽草酸完全溶解在反应体系中。随后的高效液相色谱-质谱分析表明，单棕榈酰氧基莽草酸作为唯一产物已形成，总转化率超过70%。结果表明，其具有抗血栓形成活性，可延长体内凝血时间和出血时间，并延长体外凝血时间。与对照组相比，大鼠治疗组和阿司匹林组的凝血酶原时间和凝血酶时间差异显著（P<0.05），活化部分凝血活酶时间差异极显著（P<0.01）。表明该产物具有抗凝活性。其机制可能是对内源性凝血的抑制和对外源性凝血的抑制共同作用，且对内源性途径的抑制作用强于对外源性途径的抑制作用。
