There is an increasing number of compounds developed to target one or more pathways involved in vasodilation. Some studies conducted with azaindole and indazole derivatives showed cardiovascular activity associated with these compounds. Fast and easy structural modification of these organic molecules can be achieved using metal complexes promoting a much larger spatial change than organic strategies, potentially leading to novel drugs. Here, we have prepared a series of complexes with a formula cis-[RuCl(L)(bpy)₂]PF₆, where L = 7-azaindole (ain), 5-azaindole (5-ain), 4-azaindole (4-ain), indazole (indz), benzimidazole (bzim) or quinoline (qui), which were characterized by spectroscopic and electrochemical techniques (CV, DPV). These compounds showed reasonable stability exhibiting photoreactivity only at low wavelength along with superoxide scavenger activity. Cytotoxicity assays indicated their low activity preliminarily supporting in vivo application. Interestingly, vasodilation assays conducted in rat aorta exhibited great activity that largely improved compared to free ligands and even better than the well-studied organic compound (BAY 41-42272), with IC₅₀ reaching 55 nM. These results have validated this strategy opening new opportunities to further develop cardiovascular agents based on metallo-bicyclic rings.

中文翻译：

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非一氧化氮基金属扩容剂：合成，反应性和生物学研究†

已经开发出越来越多的化合物来靶向血管舒张中涉及的一种或多种途径。用氮杂吲哚和吲唑衍生物进行的一些研究表明，与这些化合物有关的心血管活性。这些金属分子的快速，容易结构修饰可以使用金属配合物实现，该配合物比有机策略促进更大的空间变化，从而有可能导致新药的出现。在这里，我们准备了一系列具有式顺式[[RuCl（L）（bpy）₂ ] PF _{6的配合物}，其中L = 7-氮杂吲哚（ain），5-氮杂吲哚（5-ain），4-氮杂吲哚（4-ain），吲唑（indz），苯并咪唑（bzim）或喹啉（qui），其特征在于光谱和电化学技术（CV，DPV）。这些化合物显示出合理的稳定性，仅在低波长下显示光反应性以及超氧化物清除剂活性。细胞毒性测定表明它们的低活性初步支持了体内应用。有趣的是，在大鼠主动脉中进行的血管舒张试验显示出强大的活性，与游离配体相比，活性大大提高，甚至优于经过充分研究的有机化合物（BAY 41-42272），IC ₅₀达到55 nM。这些结果证实了该策略为进一步开发基于金属双环的心血管药物开辟了新的机会。