Antihypertensive profile of 2-thienyl-3,4-methylenedioxybenzoylhydrazone is mediated by activation of the A2A adenosine receptor

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 A2A adenosine receptors. Docking studies and binding assays suggested that LASSBio-1027 has affinity for A2A and A3 adenosine receptors. This new N-acylhydrazone derivative represents a potential strategy for the treatment of arterial hypertension.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► The new N-acylhydrazone derivative 2-thienyl-3,4-methylenedioxybenzoylhydrazone (LASSBio-1027) was successfully synthesized. ► LASSBio-1027 is an innovative compound and does not have structural similarity to adenosine. ► LASSBio-1027 exhibited vasodilator and antihypertensive actions. ► The molecular docking was performed in the crystal structure of A2A and A3 adenosine receptors. ► Binding assays revealed that LASSBio-1027 is a novel A2A and A3 adenosine agonist.