Shi Q, Chen K, Morris-Natschke S L, Lee K H
Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill 27599, USA.
Curr Pharm Des. 1998 Jun;4(3):219-48.
Tubulin protein is a major target of drug molecules, and consequently, tubulin inhibitors have attracted great attention as antimitotic antitumor agents for chemotherapeutic use. Hundreds of synthetic or semisynthetic tubulin inhibitors have been discovered and developed recently that are related to the natural products colchicine, vinblastine, and taxol. Representatives include allothiocolchicinoids, vinorelbine, and taxotere. This review will describe the recent progress being made in the development of novel antimitotic antitumor tubulin inhibitors. The emphasis has been placed on related research in the author's laboratory, including development of colchicine derivatives and other colchicine binding site drugs, such as flavonoids and quinolone derivatives. Syntheses and modifications of novel compounds, biological activity evaluation, and structural activity relationships will be discussed as well. Further research will undoubtedly lead to the discovery of additional tubulin inhibitors that have potential for use as anticancer drugs.
微管蛋白是药物分子的主要靶点，因此，微管蛋白抑制剂作为用于化疗的抗有丝分裂抗肿瘤药物备受关注。最近已发现并开发了数百种与天然产物秋水仙碱、长春碱和紫杉醇相关的合成或半合成微管蛋白抑制剂。代表药物包括别秋水仙碱类、长春瑞滨和多西他赛。本综述将描述新型抗有丝分裂抗肿瘤微管蛋白抑制剂开发方面的最新进展。重点将放在作者实验室的相关研究上，包括秋水仙碱衍生物及其他秋水仙碱结合位点药物（如黄酮类和喹诺酮衍生物）的开发。还将讨论新型化合物的合成与修饰、生物活性评估以及构效关系。毫无疑问，进一步的研究将发现更多有潜力用作抗癌药物的微管蛋白抑制剂。
