2- 胺基與 2’- 胺基 Combretastatins 衍生物做為強效抗有絲分裂劑
2-Amino and 2’-Aminocombretastatins Derivatives as Potent Antimitotic Agents
中文摘要
我們合成2-amino 和 2’-aminocombretastatins 一系列新穎的衍生物來探討其抗癌活性。其 中某些化合物用於抑制微小管聚合化，有不錯的抑制癌細胞生長的活性。
化合物1，11，12 抑制微小管聚合化的能力優於秋水仙鹼，其 IC50 濃度分別為
1.6，1.7，1.8 M ，有與CA4 類似的活性。在不同器官的癌細胞株試驗方面，也有良好的抑制 癌細胞增生的能力，IC50 濃度範圍大致在 11-44 nM。
根據SAR 的比較，我們發現此一系列的化合物，其 2 號位置的胺基取代，無論是在 combretastatins 的 A 環或 B 環，對於活性的影響皆有相當的重要性。
英文摘要
A novel series of 2-amino and 2’-aminocombretastatins derivatives was synthesized and evaluated for antitumor activity. Several compounds had excellent antiproliferative activity as inhibitors of tubulin polymerization.
Compound 1, 11, and 12 with IC50 of 1.6, 1.7, and 1.8 M, respectively, exhibited more potent inhibition of tubulin polymerization than colchicine and
approximately as active as CA4. They also displayed antiproliferative activity with an IC50 values ranging from 11 to 44 nM in a variety of human cancer cell lines from different organs.
SAR information indicates that the amine substituent at 2-position of ring A or ring B in combretastatin moiety plays an important role in the activity of
this series of compounds.
