Vanucci-Bacqué Corinne, Carayon Chantal, Bernis Corinne, Camare Caroline, Nègre-Salvayre Anne, Bedos-Belval Florence, Baltas Michel
Université Paul Sabatier Toulouse III, UMR 5068, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, 118, Route de Narbonne, F-31062 Toulouse Cedex 9, France; CNRS, UMR 5068, Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, 118, Route de Narbonne, F-31062 Toulouse Cedex 9, France.
INSERM, UMR 1048, I2MC, BP 84225, 31432 Toulouse Cedex 4, France.
Bioorg Med Chem. 2014 Aug 1;22(15):4269-76. doi: 10.1016/j.bmc.2014.05.034. Epub 2014 May 23.
A novel series of hydrazones derived from substituted benzaldehydes have been synthesized as potential antiatherogenic agents. Several methods were used for exploring their antioxidant and cytoprotective properties, such as their scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, the inhibition of superoxide anion (O₂(·-)) generation and the measurement of cell-induced low-density lipoprotein oxidation (monitored by the formation of TBARS). The cytoprotective efficacy was also evaluated by measuring the cell viability (monitored by the MTT assay) in the presence of cytotoxic oxidized LDL. In this report, we discuss the relationship between the chemical structure of phenolic hydrazones and their antioxidant and cytoprotective activities, for subsequent application as antiatherogenic agents. This SAR study confirms that the phenolic frame is not the only prerequisite for antioxidant activity and N-methylbenzothiazole hydrazone moiety magnifies the dual required properties in two most interesting derivatives.
已合成了一系列源自取代苯甲醛的新型腙类化合物，作为潜在的抗动脉粥样硬化药物。采用了多种方法来探究它们的抗氧化和细胞保护特性，例如它们对2,2-二苯基-1-苦基肼（DPPH）自由基的清除作用、对超氧阴离子（O₂(·-)）生成的抑制作用以及对细胞诱导的低密度脂蛋白氧化的测定（通过硫代巴比妥酸反应物（TBARS）的形成进行监测）。还通过在细胞毒性氧化型低密度脂蛋白存在的情况下测量细胞活力（通过MTT法监测）来评估细胞保护功效。在本报告中，我们讨论了酚腙的化学结构与其抗氧化和细胞保护活性之间的关系，以便后续作为抗动脉粥样硬化药物应用。该构效关系研究证实，酚环结构并非抗氧化活性的唯一先决条件，并且N-甲基苯并噻唑腙部分在两种最具吸引力的衍生物中增强了所需的双重特性。
