Synthesis of heterocycle-based analogs of resveratrol and their antitumor and vasorelaxing properties

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• 作者：Simone Bertini ; Vincenzo Calderone ; Isabella Carboni ; Roberta Maffei ; Alma Martelli ; Adriano Martinelli ; Filippo Minutolo ; Mehdi Rajabi ; Lara Testai ; Tiziano Tuccinardi ; Riccardo Ghidoni ; Marco Macchi
• 关键词：Resveratrol ; Antitumor ; Vasorelaxing ; Potassium channels ; Heterocycles
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2010
• 出版时间：15 September 2010
• 年：2010
• 卷：18
• 期：18
• 页码：6715-6724
• 全文大小：898 K

文摘

New resveratrol (RES) analogs were developed by replacing the aromatic ‘core’ of our initial naphthalene-based RES analogs with pseudo-heterocyclic (salicylaldoxime) or heterocyclic (benzofuran, quinoline, and benzothiazole) scaffolds. The resulting analogs were tested for their antiproliferative and vasorelaxing effect, two typical properties shown by RES. Some of the new compounds confirmed strong antiproliferative activities, comparable to that previously found with the most active naphthalene-based analog. In particular, 3-(3,5-dihydroxyphenyl)-7-hydroxyquinoline exhibited the most potent antiproliferative effect (IC₅₀ = 17.4 μM). In vascular assays, the highest levels of potency (pIC₅₀ = 4.92) and efficacy (E_max = 88.2 % ) were obtained with 2-(3,5-dihydroxyphenyl)-6-hydroxybenzothiazole. A conformational analysis of these compounds indicated that the antiproliferative activity on MDA-MB-231 cancer cells can be correlated to a common sterical profile of the most active compounds and, in particular, to the spatial arrangement of the three phenolic groups. Furthermore, the vasorelaxing properties showed a good correlation with the electronic properties measured through the electrostatic molecular potential (ESP).