title: 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.
authors.affiliation: Department of Chemistry, Federal Institute of Bahia, Salvador, 40301-150, Brazil.
authors.forename: Denise S
authors.initials: DS
authors.lastname: Sá
authors.forename: André F
authors.initials: AF
authors.lastname: Fernandes
authors.forename: Carlos D S
authors.initials: CD
authors.lastname: Silva
authors.forename: Paula P C
authors.initials: PP
authors.lastname: Costa
authors.forename: Manassés C
authors.initials: MC
authors.lastname: Fonteles
authors.forename: Nilberto R F
authors.initials: NR
authors.lastname: Nascimento
authors.forename: Luiz G F
authors.initials: LG
authors.lastname: Lopes
authors.forename: Eduardo H S
authors.initials: EH
authors.lastname: Sousa
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001372:Aza Compounds / Q000737:chemistry / Q000494:pharmacology; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D007191:Indazoles / Q000737:chemistry* / Q000494:pharmacology; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D012428:Ruthenium / Q000737:chemistry* / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000737:chemistry* / Q000494:pharmacology
chemical_list: C522780:4-azaindole; C512290:5-azaindole; C023422:7-azaindole dimer; D001372:Aza Compounds; D001562:Benzimidazoles; D007191:Indazoles; D007211:Indoles; D009942:Organometallic Compounds; D011804:Quinolines; D014665:Vasodilator Agents; C103599:bis(bipyridyl)ruthenium(II); D013481:Superoxides; D015082:2,2'-Dipyridyl; D012428:Ruthenium; C031000:benzimidazole; C037219:quinoline