Wolff J, Knipling L
Laboratory of Biochemical Pharmacology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Biochemistry. 1993 Dec 7;32(48):13334-9. doi: 10.1021/bi00211a047.
Chelidonine, sanguinarine, and chelerythrine are natural benzophenanthridine alkaloids that inhibit taxol-mediated polymerization of rat brain tubulin in the micromolar range. Chelidonine is a weak, competitive inhibitor of colchicine binding to tubulin but does not inhibit podophyllotoxin binding. On the other hand, sanguinarine inhibits both colchicine and podophyllotoxin binding to tubulin with I50 values of 32 and 46 microM, respectively, and chelerythrine inhibits with I50 values of 55 and 60 microM, respectively. The inhibition by these two agents is of the mixed type. Tubulin forms an acid-reversible pseudobase with the imminium ion of sanguinarine, probably through several of its sulfhydryl groups, as shown by the loss of the yellow color of sanguinarine and its 596-nm fluorescence emission peak. Chelidonine, on the other hand, cannot undergo such pseudobase formation, and we conclude that it acts by a different mechanism. A number of previously described pharmacologic effects of these agents may be due to their inhibition of microtubule function.
白屈菜碱、血根碱和白屈菜红碱是天然的苯并菲啶生物碱，它们在微摩尔范围内抑制紫杉醇介导的大鼠脑微管蛋白聚合。白屈菜碱是秋水仙碱与微管蛋白结合的弱竞争性抑制剂，但不抑制鬼臼毒素结合。另一方面，血根碱抑制秋水仙碱和鬼臼毒素与微管蛋白的结合，其半数抑制浓度（I50）值分别为32和46微摩尔，白屈菜红碱的抑制I50值分别为55和60微摩尔。这两种药物的抑制作用属于混合型。微管蛋白与血根碱的亚胺离子形成一种酸可逆的假碱，可能是通过其几个巯基，这表现为血根碱黄色的消失及其596纳米荧光发射峰的消失。另一方面，白屈菜碱不能形成这种假碱，我们得出结论，它通过不同的机制起作用。这些药物先前描述的许多药理作用可能是由于它们对微管功能的抑制。
