Synthesis and biological assessment of novel N-(hydroxy/methoxy)alkyl β-enaminone curcuminoids

详细信息    查看全文

• 作者：Atiruj Theppawong^a ; Rob De Vreese^a ; Lore Vannecke^a ; Charlotte Grootaert^b ; John Van Camp^b ; ^{John.VanCamp@UGent.be" class="auth_mail" title="E-mail the corresponding author} ; Matthias D&rsquo ; hooghe^a ; ^{matthias.dhooghe@Ugent.be" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Curcumin ; β-Enaminones ; Dihydropyridin-4-ones ; Synthesis ; Cytotoxicity ; Oxidative stress
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 December 2016
• 年：2016
• 卷：26
• 期：23
• 页码：5650-5656
• 全文大小：610 K

文摘

Curcumin, a natural compound extracted from the rhizomes of Curcuma Longa, is known to display pronounced anticancer activity but lacks good pharmacokinetic properties. In that respect, augmenting the water solubility by structural modification of the curcumin scaffold may result in improved bioavailability and pharmacokinetics. A possible scaffold modification, especially important for this study, concerns the imination of the labile β-diketone moiety in curcumin. Previous work revealed that novel N-alkyl β-enaminones showed a similar water solubility as compared to curcumin, accompanied by a stronger anti-proliferative activity. To extend this β-enaminone compound library, new analogues were prepared in this work using more polar amines (hydroxyalkylamines and methoxyalkylamines instead of alkylamines) with the main purpose to improve the water solubility without compromising the biological activity of the resulting curcuminoids. Compared to their respective parent compounds, i.e. curcumin and bisdemethoxycurcumin, the bisdemethoxycurcumin N-(hydroxy/methoxy)alkyl enaminone analogues showed better water solubility, antioxidant and anti-proliferative activities. In addition, the curcumin enaminones displayed activities comparable to or better than curcumin, and the water solubility was improved significantly. The constructed new analogues may thus be of interest for further exploration concerning their impact on oxidative stress related diseases such as cancer.