Quercetin derivatives as novel antihypertensive agents: Synthesis and physiological characterization.

摘要: The antihypertensive flavonol quercetin (Q1) is endowed with a cardioprotective effect against myocardial ischemic damage. Q1 inhibits angiotensin converting enzyme activity, improves vascular relaxation, and decreases oxidative stress gene expression. However, the clinical application of this limited by its poor bioavailability low stability in aqueous medium. In aim to overcome these drawbacks preserve effects quercetin, present study reports on preparation five different analogs, which all OH groups were replaced hydrophobic functional moieties. Q1 derivatives have been synthesized optimizing previously reported procedures analyzed spectroscopic analysis. cardiovascular properties obtained compounds also investigated order evaluate whether chemical modification affects their biological efficacy. interaction β-adrenergic receptors was evaluated molecular docking efficacy ex vivo Langendorff perfused rat heart. Furthermore, most active derivative vitro studies administration (1 month) spontaneously hypertensive rats (SHRs), respectively. Among studied derivatives, only ethyl reduced left ventricular pressure (at 10− 8 M ÷ 6 doses) improved relaxation coronary dilation. NOSs inhibition L-NAME abolished inotropism, lusitropism effects. Chronic high doses compound SHR systolic diastolic pressure. Differently, acetyl induced negative inotropism 10 doses), without affecting Accordingly, suggested that bind both β1/β2-adrenergic receptors. Taking into consideration results, replacement seems improve stability; therefore, could represent good candidate for use hypertension.