Vanucci-Bacqué Corinne, Camare Caroline, Carayon Chantal, Bernis Corinne, Baltas Michel, Nègre-Salvayre Anne, Bedos-Belval Florence
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, UMR1048, I2MC, BP 84225, 31432 Toulouse Cedex 4, France.
Bioorg Med Chem. 2016 Aug 15;24(16):3571-8. doi: 10.1016/j.bmc.2016.05.067. Epub 2016 May 30.
A series of bis-hydrazones derived from diaryl and diaryl ether hydroxybenzaldehyde frames 1 and 2 have been synthesized as potential antioxidant and antiangiogenic agents, two properties required to limit atherogenesis and cardiovascular events. These compounds were evaluated for their ability to neutralize free radical formation, to block endothelial cell-induced low-density lipoprotein oxidation (monitored by the formation of TBARS), an essential step in atherogenesis, and subsequent toxicity, to prevent angiogenesis evoked by low oxidized LDL concentration (monitored by the formation of capillary tubes on Matrigel) and to inhibit intracellular ROS increase involved in the angiogenic signaling. A structure/activity study has been carried out and finally allowed to select the phenolic diaryl ether hydralazine derivative 2a, sharing all these protective properties, as a promising hit for further development.
一系列源自二芳基和二芳基醚羟基苯甲醛骨架1和2的双腙已被合成，作为潜在的抗氧化剂和抗血管生成剂，这是限制动脉粥样硬化和心血管事件所需的两种特性。对这些化合物进行了评估，以确定它们中和自由基形成的能力、阻断内皮细胞诱导的低密度脂蛋白氧化（通过硫代巴比妥酸反应物的形成进行监测）的能力，这是动脉粥样硬化中的一个关键步骤，以及随后的毒性，以防止低氧化低密度脂蛋白浓度引起的血管生成（通过基质胶上毛细管的形成进行监测），并抑制血管生成信号传导中涉及的细胞内活性氧增加。已经进行了结构/活性研究，最终选择了具有所有这些保护特性的酚类二芳基醚肼衍生物2a，作为进一步开发的有前景的候选物。
