Cytotoxic and apoptotic activities of diarylheptanoids and gingerol-related compounds from the rhizome of Chinese ginger.
Ginger is one of the most widely used spices and has been used in traditional oriental medicines for long time. Its extract and major pungent principles have been shown to exhibit a variety of biological activities. In order to find more active constituents and evaluate their structure-activity relationship (SAR) we isolated from the rhizomes of Chinese ginger (Zingiber officinale Roscoe) five new diarylheptanoids along with 20 known diarylheptanoids and gingerol-related compounds and studied their cytotoxic and apoptotic activities against human promyelocytic leukemia (HL-60) cells. It was found that compounds 1a, 2a, 5, 6a, 6b and 7 possess significant cytotoxicity against HL-60 cells (IC(50)<50 microM) and that the cytotoxic activity is associated with the cell apoptosis. SAR analysis demonstrates that the following structural determinants contribute critically to the enhancement of the activity: (i) acetoxyl groups at 3- and/or 5-positions of the side chain; (ii) the appropriate longer alkyl side-chain length; (iii) the ortho-diphenoxyl functionality on the aromatic ring; (iv) the alpha,beta-unsaturated ketone moiety in the side chain. These provide useful information for potential chemopreventive drug design.
Wei
Qing-Yi
QY
National Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, China.
Ma
Jian-Ping
JP
Cai
Yu-Jun
YJ
Yang
Li
L
Liu
Zhong-Li
ZL
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002396:Catechols; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D036381:Diarylheptanoids / Q000494:pharmacology*; D005233:Fatty Alcohols / Q000494:pharmacology*; D005434:Flow Cytometry; D020939:Zingiber officinale / Q000737:chemistry*; D018922:HL-60 Cells; D006801:Humans; D027343:Rhizome / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000972:Antineoplastic Agents, Phytogenic; D002396:Catechols; D036381:Diarylheptanoids; D005233:Fatty Alcohols; C007845:gingerol