Antihypertensive profile of 2-thienyl-3,4-methylenedioxybenzoylhydrazone is mediated by activation of the A(2A) adenosine receptor

作者：Leal Carla Moreira; Pereira Sharlene Lopes; Kuemmerle Arthur Eugen; Leal Daniella Moreira; Tesch Roberta; de Sant' Anna Carlos M R; Fraga Carlos Alberto M; Barreiro Eliezer Jesus; Sudo Roberto Takashi; Zapata Sudo Gisele^*

来源：European Journal of Medicinal Chemistry, 2012, 55: 49-57.

DOI：10.1016/j.ejmech.2012.06.056

• N-acylhydrazone
• LASSBio-1027
• Vasodilator
• Antihypertensive
• Adenosine agonist

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.

• 出版日期2012-9