Potent vasorelaxant analogs from chemical modification and biotransformation of?isosteviol

详细信息    查看全文

• 作者：Orawan Wonganan^a ; Chainarong Tocharus^b ; Chonticha Puedsing^b ; Sureeporn Homvisasevongsa^c ; Oratai Sukcharoen^d ; Apichart Suksamrarn^a ; ^{s_apichart@ru.ac.th} ; ^{asuksamrarn@yahoo.com}
• 关键词：Isosteviol ; Vasorelaxant activity ; Biotransformation
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：April, 2013
• 年：2013
• 卷：62
• 期：Complete
• 页码：771-776
• 全文大小：389 K

文摘

Isosteviol (1) has been reported to exhibit moderate vasorelaxant activity. In order to enhance the bioactivity of this compound, chemical modification of 1 to the dihydro analog, ent-16¦Â-hydroxybeyeran-19-oic acid (2), was undertaken. Compound 2 was then converted to the corresponding acetate derivative, ent-16¦Â-acetoxybeyeran-19-oic acid (3). Biotransformation of compounds 1-3 by the fungus Cunninghamella echinulata NRRL 1386 was investigated and the metabolites 4-9 were obtained. The substrates and their metabolites were subjected to in?vitro rat aorta relaxant activity evaluation. The metabolite 4, ent-7¦Á-hydroxy-16-ketobeyeran-19-oic acid, exhibited the most highly potent activity, with EC₅₀ of 3.46?nM, whereas the parent compound 1 showed relatively low activity (EC₅₀ 57.41?nM). A 17-fold increase in vasorelaxant activity of the analog 4 relative to compound 1 is of particular significant. Compound 4 exerted vasorelaxant activity at particularly low concentration and the vasorelaxant profile reached maximum at relatively low concentration, especially when compared with acetylcholine, the positive control.