Abstract:
Andrographis paniculata Nees. (Acanthaceae), a Thai medicinal plant, is used for the treatment of cold, fever, laryngitis and infection in many Asian countries. The extract of the plant is a rich source of labdane diterpenoids and flavonoids. In continuation of our drug
discovery program on A. paniculata, we isolated the second diterpenoid component, 14-deoxy-11,12-didehydroandrographolide (2) from the aerial part of this plant and modified the structure by chemical reactions. Twenty-one derivatives were obtained in good to excellent
yields via silylation reaction at C-19 hydroxyl group, acetylation at C-3 hydroxyl group and epoxidation at C-8 alkene of (2) and thirty-seven derivatives of (2) were prepared via esterification at C-19 hydroxyl group, acetylation at C-3 in moderate to excellent yields. A
number of the 14-deoxy-11,12-didehydroandrographolide analogues showed much higher cytotoxic activity than that of the parent compound (2) on cancer cells including P-388, KB,HT29, MCF-7, LU-1, ASK, KKU M-213, HUCCA-1 and KKU-100. SAR studies of the
synthetic analogues indicated that the introduction of silyl ether or triphenyl methyl ether group in to C-19 of the parent compound led to the increasing in cytoxicity against the cancer cell. Compounds (5a) and (5b) were identified as the most potent with ED50 values of 3.37
and 3.08 M in KKU M-213 cell line and 2.93 and 3.27 in K-100 cell line respectively, than the potent anti-cancer drug ellipticine. There analogues may serve as a potential structure lead for the development of new anticancer drugs
