紫杉醇（泰素）的2-酰基类似物的合成及生物学评价

Synthesis and biological evaluation of 2-acyl analogues of paclitaxel (Taxol).

作者信息

Kingston D G, Chaudhary A G, Chordia M D, Gharpure M, Gunatilaka A A, Higgs P I, Rimoldi J M, Samala L, Jagtap P G, Giannakakou P, Jiang Y Q, Lin C M, Hamel E, Long B H, Fairchild C R, Johnston K A

机构信息

Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 4000, Princeton, New Jersey 05843, USA.

出版信息

J Med Chem. 1998 Sep 10;41(19):3715-26. doi: 10.1021/jm980229d.

DOI:10.1021/jm980229d

PMID:9733497

Abstract

The anticancer drug paclitaxel (Taxol) has been converted to a large number of 2-debenzoyl-2-aroyl derivatives by three different methods. The bioactivities of the resulting analogues were determined in both tubulin polymerization and cytotoxicity assays, and several analogues with enhanced activity as compared with paclitaxel were discovered. Correlation of cytotoxicity in three cell lines with tubulin polymerization activity showed reasonable agreement. Among the cell lines examined, the closest correlation with antitubulin activity was observed with a human ovarian carcinoma cell line.

摘要

抗癌药物紫杉醇（泰素）已通过三种不同方法转化为大量的2-脱苯甲酰基-2-芳酰基衍生物。在微管蛋白聚合和细胞毒性测定中测定了所得类似物的生物活性，并且发现了几种与紫杉醇相比活性增强的类似物。三种细胞系中的细胞毒性与微管蛋白聚合活性的相关性显示出合理的一致性。在所检查的细胞系中，在人卵巢癌细胞系中观察到与抗微管蛋白活性的最密切相关性。