82547-07-7Relevant articles and documents
Quercetin derivatives as novel antihypertensive agents: Synthesis and physiological characterization
Grande, Fedora,Parisi, Ortensia I.,Mordocco, Roberta A.,Rocca, Carmine,Puoci, Francesco,Scrivano, Luca,Quintieri, Anna M.,Cantafio, Patrizia,Ferla, Salvatore,Brancale, Andrea,Saturnino, Carmela,Cerra, Maria C.,Sinicropi, Maria S.,Angelone, Tommaso
, p. 161 - 170 (2015/12/11)
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 and gene expression. However, the clinical application of this flavonol is limited by its poor bioavailability and low stability in aqueous medium. In the aim to overcome these drawbacks and preserve the cardioprotective effects of quercetin, the present study reports on the preparation of five different Q1 analogs, in which all OH groups were replaced by hydrophobic functional moieties. Q1 derivatives have been synthesized by optimizing previously reported procedures and analyzed by spectroscopic analysis. The cardiovascular properties of the obtained compounds were also investigated in order to evaluate whether chemical modification affects their biological efficacy. The interaction with β-adrenergic receptors was evaluated by molecular docking and the cardiovascular efficacy was investigated on the ex vivo Langendorff perfused rat heart. Furthermore, the bioavailability and the antihypertensive properties of the most active derivative were evaluated by in vitro studies and in vivo administration (1 month) on spontaneously hypertensive rats (SHRs), respectively. Among all studied Q1 derivatives, only the ethyl derivative reduced left ventricular pressure (at 10- 8 M ÷ 10- 6 M doses) and improved relaxation and coronary dilation. NOSs inhibition by L-NAME abolished inotropism, lusitropism and coronary effects. Chronic administration of high doses of this compound on SHR reduced systolic and diastolic pressure. Differently, the acetyl derivative induced negative inotropism and lusitropism (at 10- 10 M and 10- 8 ÷ 10- 6 M doses), without affecting coronary pressure. Accordingly, docking studies suggested that these compounds bind both β1/β2-adrenergic receptors. Taking into consideration all the obtained results, the replacement of OH with ethyl groups seems to improve Q1 bioavailability and stability; therefore, the ethyl derivative could represent a good candidate for clinical use in hypertension.
Regioselective iodination of flavonoids by N-iodosuccinimide under neutral conditions
Lu, Kui,Chu, Jie,Wang, Haomeng,Fu, Xiaoli,Quan, Dewu,Ding, Hongxia,Yao, Qingwei,Yu, Peng
supporting information, p. 6345 - 6348 (2013/11/06)
Regioselective synthesis of C-6 and C-8 monoiodo flavonoids, which are important intermediates for the synthesis of flavonoid natural products and drug molecules, was achieved by iodination of suitably alkylated flavonoids with N-iodosuccinimide (NIS) in DMF. The iodination gives either a C-6 or C-8 iodo flavonoid in high yield, depending on the protection pattern of the C-5 and C-7 OH groups. The mild and neutral conditions render this novel protocol particularly useful for the regioselective iodination of acid-sensitive substrates.
Pentasubstituted quercetin analogues as selective inhibitors of particulate 3':5'-cyclic-AMP phosphodiesterase from rat brain
Picq,Prigent,Nemoz,Andre,Pacheco
, p. 1192 - 1198 (2007/10/02)
Some penta-O-substituted analogues of quercetin were synthesized and tested for the inhibition of cytosolic and particulate rat brain cyclic AMP and cyclic GMP phosphodiesterase activities. Ten of these compounds are potent and highly selective inhibitors of cAMP hydrolysis with respect to cGMP hydrolysis. They inhibit more potently the particulate enzyme than the cytosolic preparation. The highest selectivity was observed with penta-O-ethylquercetin and analogue 6d, which proved to be more selective and more potent inhibitors than the reference compound Ro 20-1724. Some structure-activity relationships are discussed.