Boschi Donatella, Tron Gian Cesare, Lazzarato Loretta, Chegaev Konstantin, Cena Clara, Di Stilo Antonella, Giorgis Marta, Bertinaria Massimo, Fruttero Roberta, Gasco Alberto
Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Via Pietro Giuria 9, 10125 Torino, Italy.
J Med Chem. 2006 May 18;49(10):2886-97. doi: 10.1021/jm0510530.
The synthesis and study of the antioxidant and vasodilator properties of a new class of phenols able to release nitric oxide are described. The products were designed through a symbiotic approach using selected phenols and selected nitrooxy and furoxan NO-donors as reference models. The antioxidant activities of the hybrid products were assessed by detecting the 2-thiobarbituric acid reactive substances (TBARS) produced in the ferrous salt/ascorbate-induced autoxidation of lipids present in microsomial membranes of rat hepatocytes. The vasodilator activity was assessed on rat aortic strips precontracted with phenylephrine. Some of the products (13, 35, 37, 60-62, 64) behave principally as vasodilators and others as antioxidants (24, 32, 72), and the two properties are relatively balanced in 19, 41, and 68. Further in vivo studies should clarify whether some of these products may become preclinical candidates for the treatment of cardiovascular disease underpinned by atheroma.
本文描述了一类能够释放一氧化氮的新型酚类化合物的抗氧化和血管舒张特性的合成与研究。这些产物是通过一种共生方法设计的，使用选定的酚类以及选定的硝氧基和呋咱氮氧化物一氧化氮供体作为参考模型。通过检测大鼠肝细胞微粒体膜中存在的脂质在亚铁盐/抗坏血酸诱导的自氧化过程中产生的2-硫代巴比妥酸反应性物质（TBARS），评估了杂化产物的抗氧化活性。在预先用去氧肾上腺素收缩的大鼠主动脉条上评估血管舒张活性。一些产物（13、35、37、60 - 62、64）主要表现为血管舒张剂，另一些则表现为抗氧化剂（24、32、72），而在19、41和68中这两种特性相对平衡。进一步的体内研究应阐明这些产物中的一些是否可能成为以动脉粥样硬化为基础的心血管疾病治疗的临床前候选药物。
