Friedman P A, Platzer E G
Biochim Biophys Acta. 1980 Jun 19;630(2):271-8. doi: 10.1016/0304-4165(80)90431-6.
The ability of mebendazole and fenbendazole to bind to tubulin in cytosolic fractions from 8-day Ascaris suum embryos was determined by inhibition studies with [3H]colchicine. Colchicine binding in the presence of 1 . 10(-6) M mebendazole was completely inhibited during a 6 h incubation period at 37 degrees C. Inhibition of colchicine binding to A. suum embryonic tubulin by mebendazole and fenbendazole appeared to be noncompetitive. The inhibition constants of mebendazole and fenbendazole for A. suum embryonic tubulin were 1.9 . 10(-8) M and 6.5 . 10(-8) M, respectively. Mebendazole and fenbendazole appeared to be competitive inhibitors of colchicine binding to bovine brain tubulin. The inhibition constants of mebendazole and fenbendazole for bovine brain tubulin were 7.3 . 10(-6) M and 1.7 . 10(-5) M, respectively. These values are 250-400 times greater than the inhibition constants of fenbendazole and mebendazole for A. suum embryonic tubulin. Differential binding affinities between nematode tubulin and mammalian tubulin for benzimidazoles may explain the selective toxicity. The importance of tubulin as a receptor for anthelmintic benzimidazoles in animal parasitic nematodes is discussed.
通过用[3H]秋水仙碱进行抑制研究，测定了甲苯咪唑和芬苯达唑与8日龄猪蛔虫胚胎胞质组分中的微管蛋白结合的能力。在37℃孵育6小时期间，1.10（-6）M甲苯咪唑存在下的秋水仙碱结合被完全抑制。甲苯咪唑和芬苯达唑对猪蛔虫胚胎微管蛋白的秋水仙碱结合抑制似乎是非竞争性的。甲苯咪唑和芬苯达唑对猪蛔虫胚胎微管蛋白的抑制常数分别为1.9.10（-8）M和6.5.10（-8）M。甲苯咪唑和芬苯达唑似乎是秋水仙碱与牛脑微管蛋白结合的竞争性抑制剂。甲苯咪唑和芬苯达唑对牛脑微管蛋白的抑制常数分别为7.3.10（-6）M和1.7.10（-5）M。这些值比芬苯达唑和甲苯咪唑对猪蛔虫胚胎微管蛋白的抑制常数大250-400倍。线虫微管蛋白和哺乳动物微管蛋白对苯并咪唑的不同结合亲和力可能解释了选择性毒性。讨论了微管蛋白作为动物寄生线虫中抗蠕虫苯并咪唑受体的重要性。
