title: Antihypertensive profile of 2-thienyl-3,4-methylenedioxybenzoylhydrazone is mediated by activation of the A2A adenosine receptor.
abstract: Several N-acylhydrazone derivatives synthesized from safrole have been found to promote intense vasodilation and antihypertensive activity. The present work describes the synthesis and antihypertensive profile of 2-thienyl-3,4-methylenedioxybenzoylhydrazone (LASSBio-1027), a new analogue of the lead compound 3,4-methylenedioxybenzoyl-2-thienylhydrazone. Thoracic aortas from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were prepared for isometric tension recording. Noninvasive blood pressure measurements were made during 14 days of intraperitoneal (10 mg/kg) or oral (20 mg/kg) administration of LASSBio-1027. LASSBio-1027 exhibited partially endothelium-dependent vasorelaxant activity, which was attenuated in the presence of l-NAME, glibenclamide, or ZM 241385. LASSBio-1027 exhibited an antihypertensive effect in SHR during 14 days of intraperitoneal or oral administration, but did not induce a hypotensive effect in normotensive WKY rats. LASSBio-1027-induced vascular relaxation of aortas from WKY rats was mediated by the activation of A(2A) adenosine receptors. Docking studies and binding assays suggested that LASSBio-1027 has affinity for A(2A) and A(3) adenosine receptors. This new N-acylhydrazone derivative represents a potential strategy for the treatment of arterial hypertension.
authors.affiliation: Programa de Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, RJ, Brazil. ludaca@uol.com.br
authors.forename: Carla Moreira
authors.initials: CM
authors.lastname: Leal
authors.forename: Sharlene Lopes
authors.initials: SL
authors.lastname: Pereira
authors.forename: Arthur Eugen
authors.initials: AE
authors.lastname: Kümmerle
authors.forename: Daniella Moreira
authors.initials: DM
authors.lastname: Leal
authors.forename: Roberta
authors.initials: R
authors.lastname: Tesch
authors.forename: Carlos M R
authors.initials: CM
authors.lastname: de Sant'Anna
authors.forename: Carlos Alberto M
authors.initials: CA
authors.lastname: Fraga
authors.forename: Eliezer Jesus
authors.initials: EJ
authors.lastname: Barreiro
authors.forename: Roberto Takashi
authors.initials: RT
authors.lastname: Sudo
authors.forename: Gisele
authors.initials: G
authors.lastname: Zapata-Sudo
mesh_terms: D058908:Adenosine A2 Receptor Agonists / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D055808:Drug Discovery; D057809:HEK293 Cells; D006801:Humans; D006835:Hydrazones / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D062105:Molecular Docking Simulation; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D011487:Protein Conformation; D051381:Rats; D043705:Receptor, Adenosine A2A / Q000737:chemistry / Q000378:metabolism*; D043684:Receptor, Adenosine A3 / Q000378:metabolism; D013876:Thiophenes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
chemical_list: C577437:2-thienyl-3,4-methylenedioxybenzoylhydrazone; D058908:Adenosine A2 Receptor Agonists; D000959:Antihypertensive Agents; D006835:Hydrazones; D043705:Receptor, Adenosine A2A; D043684:Receptor, Adenosine A3; D013876:Thiophenes