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具有多种心血管疾病联合作用的新型亚硝酰钌配合物。

New nitrosyl ruthenium complexes with combined activities for multiple cardiovascular disorders.

机构信息

Laboratory of Bioinorganic Chemistry, Department of Organic and Inorganic Chemistry, Federal University of Ceara, 60455-760, Fortaleza-CE, Brazil.

Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceara, Coronel Nunes de Melo St., 1127, 60.430-275, Fortaleza-CE, Brazil.

出版信息

Dalton Trans. 2023 Apr 25;52(16):5176-5191. doi: 10.1039/d3dt00059a.

Abstract

Nitrosyl ruthenium complexes are promising platforms for nitric oxide (NO) and nitroxyl (HNO) release, which exert their therapeutic application. In this context, we developed two polypyridinic compounds with the general formula -[Ru(NO)(bpy)(L)], where L is an imidazole derivative. These species were characterized by spectroscopic and electrochemical techniques, including XANES/EXAFS experiments, and further supported by DFT calculations. Interestingly, assays using selective probes evidenced that both complexes can release HNO on reaction with thiols. This finding was biologically validated by HIF-1α detection. The latter protein is related to angiogenesis and inflammation processes under hypoxic conditions, which is selectively destabilized by nitroxyl. These metal complexes also presented vasodilating properties using isolated rat aorta rings and demonstrated antioxidant properties in free radical scavenging experiments. Based on these results, the new nitrosyl ruthenium compounds showed promising characteristics as potential therapeutic agents for the treatment of cardiovascular conditions such as atherosclerosis, deserving further investigation.

摘要

亚硝酰钌配合物是一氧化氮 (NO) 和硝酰自由基 (HNO) 释放的有前途的平台,它们发挥着治疗作用。在这种情况下,我们开发了两种具有通式-[Ru(NO)(bpy)(L)]的聚吡啶化合物,其中 L 是咪唑衍生物。这些物质通过光谱和电化学技术进行了表征,包括 XANES/EXAFS 实验,并通过 DFT 计算进一步支持。有趣的是,使用选择性探针的测定表明,这两种配合物都可以在与巯基反应时释放 HNO。这一发现通过 HIF-1α 的检测得到了生物学验证。后者的蛋白质与缺氧条件下的血管生成和炎症过程有关,硝酰自由基选择性地使它失稳。这些金属配合物还在分离的大鼠主动脉环中表现出舒张血管的特性,并在自由基清除实验中表现出抗氧化特性。基于这些结果,新的亚硝酰钌化合物作为治疗动脉粥样硬化等心血管疾病的潜在治疗剂表现出有希望的特性,值得进一步研究。

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