1.Prevention of cardiac dysfunction, kidney fibrosis and lipid metabolic alterations in l-NAME hypertensive rats by sinapic acid-Role of HMG-CoA reductase.
Silambarasan T1, Manivannan J2, Raja B3, Chatterjee S4. Eur J Pharmacol. 2016 Apr 15;777:113-23. doi: 10.1016/j.ejphar.2016.03.004. Epub 2016 Mar 2.
The present study was designed to evaluate the effect of sinapic acid, a bioactive phenolic acid on high blood pressure associated cardiac dysfunction, kidney fibrosis and lipid alterations in N(ω)-nitro-l-arginine methyl ester hydrochloride (l-NAME) induced hypertensive rats. Sinapic acid was administered to rats orally at a dosage of 40mg/kg everyday for a period of 4 weeks. Sinapic acid treatment significantly decreased mean arterial pressure, left ventricular end diastolic pressure, organ weights (liver and kidney), lipid peroxidation products in tissues (liver and kidney), activities of hepatic marker enzymes and the levels of renal function markers in serum of l-NAME rats. Sinapic acid treatment also significantly increased the level of plasma nitric oxide metabolites, and enzymatic and non-enzymatic antioxidants in tissues of l-NAME rats. Tissue damage was assessed by histopathological examination. Alterations in plasma angiotensin-converting enzyme activity, level of plasma lipoproteins and tissue lipids were corrected by sinapic acid treatment in l-NAME rats.
2.Lipopolysaccharide Delays Closure of the Rat Ductus Arteriosus by Induction of Inducible Nitric Oxide Synthase But Not Prostaglandin E2.
Kajimura I1, Akaike T, Minamisawa S. Circ J. 2016 Feb 25;80(3):703-11. doi: 10.1253/circj.CJ-15-1053. Epub 2016 Jan 27.
BACKGROUND: The incidence of patent ductus arteriosus is known to be higher in premature neonates with infection than in those without infection. However, the detailed mechanism has not been investigated.
3.Design, synthesis and biological evaluation of 6-substituted pyrrolo[2,3-d]pyrimidines as dual inhibitors of TS and AICARFTase and as potential antitumor agents.
Liu Y1, Li M2, Zhang H2, Yuan J2, Zhang C2, Zhang K2, Guo H1, Zhao L1, Du Y2, Wang L3, Ren L4. Eur J Med Chem. 2016 Jun 10;115:245-56. doi: 10.1016/j.ejmech.2016.03.032. Epub 2016 Mar 21.
A new series of 2-amino-4-oxo-6-substituted pyrrolo[2,3-d]pyrimidines, with an isosteric replacement of the side chain amide moiety to a sulfur atom, were designed and synthesized as multitargeted antifolates as well as potential antitumor agents. Starting from previously synthesized 2-amino-4-oxo-pyrrolo[2,3-d]pyrimidin-6-yl-acetic acid, a reduction by lithium triethylborohydride and successive mesylation afforded the key mesylate. Nucleophilic substitution by mercaptoacetic or mercaptopropionic acid methyl esters, followed by hydrolysis and condensation with pyridinyl-methylamines provided the nonclassical compounds 1-6, whereas condensation with glutamic acid diethyl ester hydrochloride and saponification afforded the classical analogs 7-8. All target compounds exhibited inhibitory activities toward KB, SW620 and A549 tumor cell lines. The most potent compounds of this series, 7 and 8, are better inhibitors against A549 cells than methotrexate (MTX) and pemetrexed (PMX).
4.Mucosal acidification increases hydrogen sulfide release through up-regulating gene and protein expressions of cystathionine gamma-lyase in the rat gastric mucosa.
Mard SA1, Veisi A2, Ahangarpour A2, Gharib-Naseri MK2. Iran J Basic Med Sci. 2016 Feb;19(2):172-7.
OBJECTIVES: This study was performed to investigate the effects of mucosal acidification on mRNA expression and protein synthesis of cystathionine gamma lyase (CSE), cystathionine beta synthase (CBS), and mucosal release of H2S in gastric mucosa in rats.
