Non-nitric oxide based metallovasodilators: synthesis, reactivity and biological studies

Abstract

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)]PF(6), 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 IC(50) reaching 55 nM. These results have validated this strategy opening new opportunities to further develop cardiovascular agents based on metallo-bicyclic rings.

Homoleptic Transition Metal Complexes of the 7-Azaindolide Ligand Featuring κ1-N1 Coordination

“…To the best of our knowledge, only one example of a transition metal complex of 4-azaindole in any protonation state has been reported previously. 62 Accordingly, four equivalents of 4-azaindole were reacted with FeCl 2 (THF) 1.5 in THF in the presence of NaHMDS. Upon addition of the base, immediate precipitation of a yellow solid was observed (eq.…”

Luminescent cis-Bis(bipyridyl)ruthenium(II) Complexes with 1,2-Azolylamidino Ligands: Photophysical, Electrochemical Studies, and Photocatalytic Oxidation of Thioethers

“…At negative potentials (0 to −1.8 V vs SCE) (see Figure S24 for 3b ), the electrochemistry of complexes 1 , 3 , and 4 is analogous to that of cis -bis(bipy)ruthenium(II) complexes and is associated with reduction processes centered at the bipyridine ligands. 23 , 73 , 77 − 79 All of the 1,2-azolylamidino complexes described herein present similar behavior (see the Supporting Information ).…”

“…The redox properties of complexes 1 have been previously described. 73 , 74 However, for 1a , c the reduction waves were not showed, for this reason we have reported them again. Moreover, herein we report the electrochemistry of the 1,2-azolylamidino complexes 3 and 4 .…”

“…As expected, this positive variation in the potential is even higher in comparison with the potential of the cis -[Ru(bipy) 2 Cl 2 ] complex. 73 , 74 …”

Is IQG-607 a Potential Metallodrug or Metallopro-Drug With a Defined Molecular Target in Mycobacterium tuberculosis?

“…Structural diversity has been explored using metals to create new compounds with a more stringent targeting of biological polymers such as proteins, DNA and RNA (Wilbuer et al, 2010 ; Meggers, 2011 ; Sa et al, 2015 ; Sousa et al, 2017 ). Some promising examples were reported using staurosporin-like ligand as a scaffold for ruthenium metal complex achieving higher biological activity and improved selectivity toward kinase inhibition (Dorr and Meggers, 2014 ).…”