Design and synthesis of ten biphenyl-neolignan derivatives and their in vitro inhibitory potency against cyclooxygenase-1/2 activity and 5-lipoxygenase-mediated LTB4-formation

被引：45

作者：

Schuehly, Wolfgang ^{[1
]}

Huefner, Antje ^{[2
]}

Pferschy-Wenzig, Eva M. ^{[1
]}

Prettner, Elke ^{[2
]}

Adams, Michael ^{[1
]}

Bodensieck, Antje ^{[1
]}

Kunert, Olaf ^{[2
]}

Oluwemimo, Asije ^{[2
]}

Haslinger, Ernst ^{[2
]}

Bauer, Rudolf ^{[1
]}

机构：

[1] Karl Franzens Univ Graz, Inst Pharmaceut Sci, Dept Pharmacognosy, A-8010 Graz, Austria

[2] Karl Franzens Univ Graz, Dept Pharmaceut Chem, Inst Pharmaceut Sci, A-8010 Graz, Austria

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 13期

关键词：

Honokiol derivatives; Cyclooxygenase; Lipoxygenase; Anti-inflammatory; SAR; DUAL INHIBITION; HONOKIOL; COX-2; ACTIVATION; EXPRESSION; MAGNOLOL; 5-LOX;

D O I：

10.1016/j.bmc.2009.05.018

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A set of ten derivatives of methylhonokiol, an anti-inflammatory active biphenyl-type neolignan from Magnolia grandiflora, has been evaluated for their in vitro cyclooxygenase-1/2 (COX-1/2) inhibitory activity using assays with purified prostaglandin H synthase (PGHS)-1 and PGHS-2 enzymes as well as for their 5-lipoxygenase (5-LOX) mediated LTB4 formation inhibitory activity using an assay with activated human polymorphonuclear leukocytes. The derivatization reactions included methylation, acetylation, hydrogenation, epoxydation and isomerization. Five of the derivatives are new to science. The most active compound against COX-1 and COX-2 was methylhonokiol with IC50 values of 0.1 mu M, whereas the most active compound against LTB4 formation was (E)-3'-propenyl-5-(2-propenyl)-biphenyl-2,4'-diol with an IC50 value of 1.0 mu M. Structure-activity relationship studies showed that the polarity of the derivatives plays a crucial role in their activity towards COX-1/2 enzyme and 5-LOX mediated LTB4 formation. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：4459 / 4465

页数：7

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