| dc.description.abstract |
Andrographolide, the major diterpenoid lactone from andrographis paniculata, is toxic Against cancer cells. In the present study, we investigated the structure-activity relationships (SAR) of 55 andrographolide analogues which were synthesized by chemical modification of the andrographolide structure. Several reactions were employed such as acetylation and silylation of the three hydroxyl groups, rearrangement of C-14 hydroxyl group, epoxidation and cyclization reactions. The cytotoxic activity of all synthetic analogues were evaluated using in vitro sulforhodamine B (SEB) assay against six cancer cell lines including P-388 (murine leukemia cell line), KB (human epidermiod carcinoma of the mouth), COL-2 (human colon cancer), MCF-7 (human breast cancer), LU-1 (human lung cancer), and ASK (rat glioma). A number of the andrographolide analogues showed buch 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 sily1 ether or triphenylmethyl ether group into C-19 of the parent compound led to increase in toxicity against the cancer cells. Some analogue showed higher cytotoxic activity than the potent anticancer drug ellipticine, and these analogue may serve as a potential structure lead for the development of new anticancer drugs. |
th_TH |