STRUCTURE MODIFICATION OF ANDROGRAPHOLIDE TO IMPROVE ITS POTENCY AS ANTICANCER
ABSTRACT: 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.
Author: Hadi Poerwono,
Yoshiyuki Hattori, Hajime Kubo and Kimio Higashiyama
Journal Code: jpkimiagg070020
