STRUCTURE MODIFICATION OF ANDROGRAPHOLIDE TO IMPROVE ITS POTENCY AS ANTICANCER

Hadi Poerwono (Faculty of Pharmacy, Airlangga University, Jl. Dharmawangsa Dalam, Surabaya 60286, Indonesia)
Yoshiyuki Hattori (Institute of Medicinal Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa, Tokyo 152-8501, Japan)
Hajime Kubo (Institute of Medicinal Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa, Tokyo 152-8501, Japan)
Kimio Higashiyama (Institute of Medicinal Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa, Tokyo 152-8501, Japan)

Indonesian Journal of Chemistry
Vol 7, No 2 (2007)

Andrographolide, a diterpenoid lactone isolated from the herb of Andrographis paniculata and known to possess antitumor activity in breast cancer models was subjected to semisynthesis leading to the preparation of a number of derivatives. After protection of the two hydroxyl groups present at C-3 and C-19 to give 3,19-isopropylidene and 3,19-benzylidene andrographolides, the remaining hydroxyl group at C-14 of andrographolide was treated with acid anhydride or acid chloride under base condition. Unfortunately, the reactions gave only 14-dehydroandrographolide as well as unidentified diacyl compounds in replace of the target molecule 14-O-acyl andrographolide. An alternative procedure using neat acetic anhydride under reflux gave the acetyl derivatives. The resulted compounds exhibited cytotoxic activity against MCF-7 breast cancer cells with better growth inhibition than the parent compound andrographolide.