Department of Chemistry and Center for Innovation in Chemistry, Faculty of Science, Burapha University, Chonburi 20131, Thailand.
Bioorg Med Chem Lett. 2012 Jan 1;22(1):49-52. doi: 10.1016/j.bmcl.2011.11.085. Epub 2011 Nov 28.
Andrographolide, the major diterpenoid lactone from Andrographis paniculata, is toxic against cancer cells. In the present study, we investigated the structure-activity relationships (SARs) of 19 andrographolide analogues which were synthesized by modification at the three hydroxyl groups. A number of the andrographolide analogues showed much higher cytotoxic activities than that of the parent compound on cancer cells including P-388, KB, COL-2, MCF-7, LU-1 and ASK cells. SAR studies of the synthetic analogues indicated that the introduction of silyl ether or triphenylmethyl ether group into C-19 of the parent compound led to increase in toxicity against the cancer cells. The 19-O-triphenylmethyl ether analogue 18 showed higher cytotoxic activity than the potent anticancer drug ellipticine, and this analogue may serve as a potential structure lead for the development of new anticancer drugs.
穿心莲内酯是穿心莲中的主要二萜内酯，对癌细胞有毒性。在本研究中，我们研究了 19 种穿心莲内酯类似物的结构-活性关系 (SAR)，这些类似物是通过在三个羟基上进行修饰合成的。一些穿心莲内酯类似物对癌细胞（包括 P-388、KB、COL-2、MCF-7、LU-1 和 ASK 细胞）的细胞毒性活性比母体化合物高得多。合成类似物的 SAR 研究表明，在母体化合物的 C-19 上引入硅醚或三苯甲基醚基团会导致对癌细胞的毒性增加。19-O-三苯甲基醚类似物 18 显示出比强效抗癌药物依利替康更高的细胞毒性活性，该类似物可能作为开发新型抗癌药物的潜在结构先导物。
