Abstract |
Based on the observed biological activities of coumarins and resveratrol, we synthesized fourteen hydroxylated 3-phenylcoumarins ( stilbene- coumarin hybrids) including six novel ortho-hydroxy-methoxy substituted derivatives, 1-14, by Perkin reaction. We characterized these compounds concerning their antioxidant activity against 2,2'-azobis(2-amidinopropane hydrochloride) ( AAPH)-induced pBR322 DNA strand breakage, and their antiproliferative effects on human promyelocytic leukemia HL-60 and human lung adenocarcinoma epithelial A549 cells. Structure-activity relationship information suggests that the introduction of ortho-hydroxy-methoxy groups and ortho-dihydroxy groups on the aromatic A ring could efficiently improve antiproliferative activity. Interestingly, a new derivative, 6-methoxy-7-hydroxy-3-(4'-hydroxyphenyl)coumarin, 9, behaved as a poor antioxidant but appeared to be the most potent antiproliferative agent among the compounds examined, and this activity was mediated by deregulation in cell cycle and induction of apoptosis.
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Authors | Jie Yang, Guo-Yun Liu, Fang Dai, Xiao-Yan Cao, Yan-Fei Kang, Li-Mei Hu, Jiang-Jiang Tang, Xiu-Zhuang Li, Yan Li, Xiao-Ling Jin, Bo Zhou |
Journal | Bioorganic & medicinal chemistry letters
(Bioorg Med Chem Lett)
Vol. 21
Issue 21
Pg. 6420-5
(Nov 01 2011)
ISSN: 1464-3405 [Electronic] England |
PMID | 21920747
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 Elsevier Ltd. All rights reserved. |
Chemical References |
- Antineoplastic Agents
- Antioxidants
- Coumarins
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Topics |
- Adenocarcinoma
(pathology)
- Antineoplastic Agents
(chemical synthesis, chemistry, pharmacology)
- Antioxidants
(chemical synthesis, chemistry, pharmacology)
- Cell Line, Tumor
- Coumarins
(chemical synthesis, chemistry, pharmacology)
- DNA Damage
- Drug Evaluation, Preclinical
- Humans
- Lung Neoplasms
(pathology)
- Structure-Activity Relationship
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