1.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.
2.Effects of midodrine and L-NAME on systemic and cerebral hemodynamics during cognitive activation in spinal cord injury and intact controls.
Wecht JM1, Weir JP2, Radulovic M3, Bauman WA3. Physiol Rep. 2016 Feb;4(3). pii: e12683. doi: 10.14814/phy2.12683.
We previously showed that increases in mean arterial pressure (MAP) following administration of midodrine hydrochloride (MH) and nitro-L-arginine methyl ester (L-NAME) resulted in increased mean cerebral blood flow velocity (MFV) during head-up tilt in hypotensive individuals with spinal cord injury (SCI) and question if this same association was evident during cognitive activation. Herein, we report MAP and MFV during two serial subtraction tasks (SSt) given before (predrug) and after (postdrug) administration of MH; (10 mg), L-NAME (1 mg/kg) or no drug (ND) in 15 subjects with SCI compared to nine able-bodied (AB) controls. Three-way factorial analysis of variance (ANOVA) models were used to determine significant main and interaction effects for group (SCI, AB), visit (MH, L-NAME, ND), and time (predrug, postdrug) for MAP and MFV during the two SSt. The three-way interaction was significant for MAP (F = 4.262; P = 0.020); both MH (30 ± 26 mmHg; P < 0.
3.Synthesis and biological evaluation of new 1,3-thiazolidine-4-one derivatives of nitro-l-arginine methyl ester.
Pânzariu AT1, Apotrosoaei M1, Vasincu IM1, Drăgan M1, Constantin S1, Buron F2, Routier S2, Profire L1, Tuchilus C3. Chem Cent J. 2016 Feb 4;10:6. doi: 10.1186/s13065-016-0151-6. eCollection 2016.
BACKGROUND: l-Arginine is a semi-essential aminoacid with important role in regulation of physiological processes in humans. It serves as precursor for the synthesis of proteins and is also substrate for different enzymes such as nitric oxide synthase. This amino-acid act as free radical scavenger, inhibits the activity of pro-oxidant enzymes and thus acts as an antioxidant and has also bactericidal effect against a broad spectrum of bacteria.
4.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).
