Abstract
Hyper-proliferation and migration of vascular smooth muscle cells and endothelial cell dysfunction are central events in the development of neo-intimal lesions. Pursuing our interest in the synthesis of bioisosters of flavonoids, we studied in depth a novel synthetic 2,3-diphenyl-4H-pyrido[1,2-a]pyrimidin-4-one derivative, examining its effects in vitro on induced-cell proliferation and activation in human aortic smooth muscle cells (HAoSMCs) and in human umbilical vein endothelial cells (HUVECs). Compared with two well known flavonoids, apigenin and quercetin, the novel compound, 2-(3,4-dimethoxyphenyl)-3-phenyl-4H-pyrido[1,2-a]pyrimidin-4-one, 3, was not toxic for HUVECs, even at high concentrations and for long incubation times, while the two flavonoids were not tolerated, even at concentrations as low as 10 μmol/L. Compound 3 inhibited selectively, and in a concentration-dependent manner, the proliferation of HAoSMCs but not that of HUVECs. In HUVECs, it inhibited the cytokine-induced vascular cell adhesion molecule-1 expression, but not the cyclooxygenase-2 (COX-2) expression. Instead, in HAoSMC, it inhibited the induction of COX-2 expression and the relative release of prostaglandin E2. In addition, it inhibited the trans...Continue Reading
References
Jun 1, 1994·Clinical Immunology and Immunopathology·O J Finn
Dec 1, 1996·Circulation Research·K M SouthgateA C Newby
Jan 22, 2000·Arthritis and Rheumatism·L J CroffordL B van de Putte
Nov 2, 2002·Circulation Research·Zorina S GalisEugen Ivan
Nov 5, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Mario Romano, Joan Claria
May 12, 2004·Current Pharmaceutical Design·Gustavo BaldassarreBarbara Belletti
Jun 15, 2004·Cardiovascular Research·Yong Woo LeeMichal Toborek
Sep 17, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Guangdong YangRui Wang
Oct 13, 2004·Mutation Research·Rana P Singh, Rajesh Agarwal
May 6, 2006·European Journal of Obstetrics, Gynecology, and Reproductive Biology·M BullarboE Ekerhovd
Jun 6, 2006·Microvascular Research·Teresa NavarraGiuseppina Basta
Feb 28, 2007·Circulation·Thomas F LüscherRenu Virmani
Aug 19, 2007·Current Medicinal Chemistry·E ArehartJ Hwa
Sep 12, 2007·Journal of Medicinal Chemistry·Concettina La MottaMario Ciuffi
Sep 18, 2007·Endocrinology·Jun KawagoeHirohisa Kurachi
Oct 30, 2007·Experimental Physiology·Jane A MitchellLouise S Harrington
Oct 30, 2007·Circulation·Stephan Windecker, Bernhard Meier
Nov 21, 2007·Heart, Lung & Circulation·Ryan G SchraleAdrian Banning
May 29, 2008·Angiology·Mehmet SahinSaadet Gümüslü
Jul 23, 2008·Perspectives in Vascular Surgery and Endovascular Therapy·Kimon Bekelis, Nicos Labropoulos
Jul 23, 2008·Circulation·Mark A Hlatky, Dena M Bravata
Aug 12, 2008·Current Drug Discovery Technologies·Nirmala Bhogal, Michael Balls
Sep 11, 2008·European Journal of Pharmacology·Woochul ChangKi-Chul Hwang
Jul 14, 2009·Arteriosclerosis, Thrombosis, and Vascular Biology·Nozomi FukaiAlexander W Clowes
Aug 6, 2009·Nitric Oxide : Biology and Chemistry·Guido LazzeriniRaffaele De Caterina
Oct 10, 2009·Integrative Cancer Therapies·Gazala N KhanSofia D Merajver
May 13, 2010·Natural Product Research·Santosh K ShuklaSuman B Sharma
Jun 24, 2010·The Proceedings of the Nutrition Society·Mauro SerafiniAnna Raguzzini
Apr 19, 2011·Current Opinion in Pharmacology·Arturo Giordano, Alfredo Romano
May 3, 2011·Circulation Journal : Official Journal of the Japanese Circulation Society·Antonio CurcioCiro Indolfi
Jun 10, 2011·Current Medicinal Chemistry·S SartiniC La Motta
Sep 14, 2011·Nature Reviews. Cardiology·J Wouter JukemaPaul H A Quax
Nov 19, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Yue ZhengMurray C H Clarke
Dec 7, 2011·Critical Reviews in Clinical Laboratory Sciences·Miguel AsensiJosé M Estrela
Dec 14, 2011·Atherosclerosis·Zhe-xue QinLan Huang
Jun 2, 2012·Journal of the American College of Cardiology·Seung-Jung ParkYasunori Ueda
Aug 15, 2012·Journal of Nutrition in Gerontology and Geriatrics·Donato F Romagnolo, Ornella I Selmin
Nov 29, 2012·Journal of Pharmaceutical Sciences·Pius FasinuViness Pillay
Aug 31, 2013·Nutrients·Surangi H Thilakarathna, H P Vasantha Rupasinghe
Sep 8, 2015·International Journal of Cardiology·Ahmad MustafaBernard Clarke