Friedman P A, Platzer E G
Biochim Biophys Acta. 1978 Dec 18;544(3):605-14. doi: 10.1016/0304-4165(78)90334-3.
The binding and inhibitory properties of 11 benzimidazoles for bovine brain tubulin were investigated. The effects of the benzimidazoles on the initial rates of microtubule polymerization were determined by a turbidimetric assay. The median inhibitory concentrations (I50) for nocodazole, oxibendazole, parbendazole, mebendazole and fenbendazole ranged from 1.97 . 10(-6) to 6.32 . 10(-6) M. Benomyl, cambendazole and carbendazim had I50 values from 5.83 . 10(-5) to 9.01 .10(-5) M. Thiabendazole had an I50 value of 5.49 . 10(-4) M. Inhibitor constants (Ki) were determined by the colchicine binding assay. Oxibendazole, fenbendazole, and cambendazole had Ki values of 3.20 . 10(-5), 1.73 . 10(-5) and 1.10 . 10(-4) M, respectively. Oxibendazole and fenbendazole were competitive inhibitors of colchicine. In contrast, cambendazole was a noncompetitive inhibitor of colchicine. The ability of these benzimidazoles to inhibit microtubule polymerization and the mode of action for the anthelmintic benzimidazoles is discussed.
研究了11种苯并咪唑对牛脑微管蛋白的结合和抑制特性。通过比浊法测定苯并咪唑对微管聚合初始速率的影响。诺考达唑、奥昔苯达唑、帕苯达唑、甲苯达唑和芬苯达唑的半数抑制浓度（I50）范围为1.97×10⁻⁶至6.32×10⁻⁶ M。苯菌灵、坎苯达唑和多菌灵的I50值为5.83×10⁻⁵至9.01×10⁻⁵ M。噻苯达唑的I50值为5.49×10⁻⁴ M。通过秋水仙碱结合试验测定抑制常数（Ki）。奥昔苯达唑、芬苯达唑和坎苯达唑的Ki值分别为3.20×10⁻⁵、1.73×10⁻⁵和1.10×10⁻⁴ M。奥昔苯达唑和芬苯达唑是秋水仙碱的竞争性抑制剂。相比之下，坎苯达唑是秋水仙碱的非竞争性抑制剂。讨论了这些苯并咪唑抑制微管聚合的能力以及驱虫苯并咪唑的作用方式。
