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Unformatted text preview: Arch Pharm Res Vol 27, No 3, 278-282, 2004 278 http://apr.psk.or.kr Synthesis and Biological Activities of 8-Arylflavones Tran Thanh Dao, Soo Bae Kim, Kwan-Seog Sin, Sanghee Kim 1 , Hyun Pyo Kim, and Haeil Park College of Pharmacy, Kangwon National University, Chuncheon 200-701, Korea and 1 College of Pharmacy, Seoul National University, Seoul 110-460, Korea (Received January 15, 2004) A number of 8-arylflavones have been synthesized as congeners of wogonin and evaluated for their inhibitory activities of PGE 2 production. 8-Arylflavones were obtained from commercially available chrysin via two different synthetic pathways. Most 8-arylflavones exhibited much reduced inhibitory activities against COX-2 catalyzed PGE 2 production compared to that of wogonin. Functional group replacement at the 8-position of wogonin from methoxy to aryl group caused loss of inhibitory activity. Our present results imply that the functional group at the 8-position of flavones seems to play very important roles for bioactivity. Key words: 8-Arylflavones, COX-2, Prostaglandin production inhibition, Anti-inflammatory activity, Suzuki reaction, Carbon-carbon coupling reaction INTRODUCTION Flavonoids are natural polyphenol compounds of plant origin and exhibit various biological activities such as anti- inflammatory, anti-oxidant, and anti-tumor activities (Read, 1995; Harborne, 2000). It has been previously reported that various plant flavonoids possess the inhibitory activity on cyclooxygenase/lipoxygenase (Wakabayashi, 2000; Chi, 2001; Chen, 2001). Some flavonoids, such as flavone derivatives, have been reported previously to inhibit nitrogen oxide (NO) production by suppressing inducible nitric oxide synthase (iNOS) expression (Wakabayashi, 1999; Chi, 2001 & 2003; Chen, 2001; Kim, 2001; Lee, 2003). And these properties of flavonoids might contribute to their anti-inflammatory activity both in vitro and in vivo . Wogonin (5,7-dihydroxy-8-methoxyflavone), a flavonoid isolated from the root of a medicinal herb Scutellaria baicalensis Georgi, has been shown to possess various anti-inflammatory activities (Wakabayashi, 1999 & 2000; Shieh, 2000; Chi, 2001 & 2003; Chen, 2001; Kim, 2001; Lee, 2003). These results led us to investigate the structural requirement of wogonin for anti-inflammatory activity. Base on the results from the structure-activity relationships of wogonin and some other naturally occurring flavonoids such as chrysin (Fig. 1), we conjectured that the methoxy functional group at 8-position of wogonin plays important roles to possess strong anti-inflammatory activity since wogonin exhibited much stronger inhibitory activity than chrysin against COX-2 catalyzed prostaglandin production from lipopolysaccharide-treated RAW 264.7 cells. In order to improve the biological activities of wogonin, we started to prepare wogonin derivatives modified 8-methoxy group of the A ring by various functional groups. In this work, we report the synthesis of 8-aryl substituted wogonin derivatives...
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This note was uploaded on 02/17/2011 for the course CHEMISTRY 101 taught by Professor Csr during the Spring '11 term at University of Louisville.
- Spring '11