Search results for "Guanidines"

Human ABCB1 confers cells resistance to cytotoxic guanidine alkaloids from Pterogyne nitens.

2015

Multidrug resistance (MDR) caused by human ABCB1 (P-glycoprotein/MDR1) is one of the major obstacles in chemotherapy. To understand the mechanism of MDR by ABCB1 and circumvent the MDR, in the present study, we established human ABCB1-expressing cells (Flp-In-293/ABCB1 cells) and examined the cytotoxic effects of four guanidine alkaloids from Pterogyne nitens (galegine, nitensidine A, pterogynidine and pterogynine) using Flp-In-293/Mock and Flp-In-293/ABCB1 cells. The activity of ABCB1 in Flp-In-293/ABCB1 cells were confirmed by typical substrates for ABCB1 (taxol and vinblastine) in MTT assay. Flp-In-293/ABCB1 cells were also resistant to the four guanidine alkaloids as well as taxol and v…

Nitensidine A, a guanidine alkaloid from Pterogyne nitens, is a novel substrate for human ABC transporter ABCB1.

2014

The Pterogyne nitens (Fabaceae) tree, native to South America, has been found to produce guanidine alkaloids as well as bioactive flavonols such as kaempferol, quercetin, and rutin. In the present study, we examined the possibility of interaction between human ATP-binding cassette (ABC) transporter ABCB1 and four guanidine alkaloids isolated from P. nitens (i.e., galegine, nitensidine A, pterogynidine, and pterogynine) using human T cell lymphoblast-like leukemia cell line CCRF-CEM and its multi-drug resistant (MDR) counterpart CEM/ADR5000. In XTT assays, CEM/ADR5000 cells were resistant to the four guanidine alkaloids compared to CCRF-CEM cells, although the four guanidine alkaloids exhibi…

Effects of Some Guanidino Compounds on Human Cerebral Arteries

1999

Background and Purpose —Accumulation of endogenous guanidino-substituted analogues of l -arginine in chronic renal failure might contribute to some of the vascular and neurological disorders of this pathology. We tested the hypothesis that in human cerebral arteries, some guanidino compounds may increase vascular tone, through nitric oxide (NO) synthase inhibition, and impair endothelium-dependent relaxation. Methods —Rings of human middle cerebral artery were obtained during autopsy of 26 patients who had died 3 to 12 hours before. The rings were suspended in organ baths for isometric recording of tension. We then studied the responses to N G -monomethyl- l -arginine (L-NMMA), N G , N G -…

Contractile effects of arginine analogues on human internal thoracic and radial arteries

2000

Abstract Objectives: Plasma levels of endogenous guanidino-substituted analogues of L -arginine are increased in various pathologic conditions. In the present study we determined the effects of some of these compounds on basal and stimulated release of nitric oxide in human internal thoracic and radial arteries. Methods: Rings of human internal thoracic and radial arteries were obtained from 16 multiorgan donors. The rings were suspended in organ baths for isometric recording of tension. Results: N G -monomethyl L -arginine (10 –6 to 10 –3 mol/L) and N G ,N G -dimethyl L -arginine (10 –6 to 10 –3 mol/L) caused concentration- and endothelium-dependent contractions. Maximal force of contracti…

Dose escalating safety study of CNS 5161 HCl, a new neuronal glutamate receptor antagonist (NMDA) for the treatment of neuropathic pain

2007

What is already known about this subject • Despite encouraging effects of N-methyl-D-aspartate (NMDA) receptor antagonists in reducing neuropathic pain of different aetiologies, the clinical use of these agents has been limited by their mainly psychotropic side-effects. • In a recent study in healthy volunteers, CNS 5161, a novel noncompetetive NMDA receptor antagonist, was well tolerated up to a dosage of 2000 µg without psychotropic side-effects. • This is the first study to evaluate the maximal tolerated dosage of CNS 5161 and to gain experience about the analgesic effect of CNS 5161 in patients with different pain syndromes. What this study adds • In patients with neuropathic pain CNS 5…

Cardioprotective Effects of the Na + /H + Exchange Inhibitor Cariporide in Patients With Acute Anterior Myocardial Infarction Undergoing Direct PTCA

2000

Background —Activation of Na + /H + exchange in myocardial ischemia and/or reperfusion leads to calcium overload and myocardial injury. Experimental studies have shown that Na + /H + exchange inhibitors can attenuate Ca 2+ influx into cardiomyocytes. We therefore performed a multicenter, randomized, placebo-controlled clinical trial to test the hypothesis that inhibition of Na + /H + exchange limits infarct size and improves myocardial function in patients with acute anterior myocardial infarction (MI) treated with direct PTCA. Methods and Results —One hundred patients were randomized to receive placebo (n=51) or a 40-mg intravenous bolus of the Na + /H + exchange inhibitor cariporide (HOE…

Host Solids Containing Nanoscale Anion-Binding Pockets and Their Use in Selective Sensing Displacement Assays

2005

Synthesis, reactivity, and computational analysis of halophosphines supported by dianionic guanidinate ligands.

2012

The reported chemistry and reactivity of guanidinate supported group 15 elements in the +3 oxidation state, particularly phosphorus, is limited when compared to their ubiquity in supporting metallic elements across the periodic table. We have synthesized a series of chlorophosphines utilizing homo- and heteroleptic (dianionic)guanidinates and have completed a comprehensive study of their reactivity. Most notable is the reluctancy of these four-membered rings to form the corresponding N-heterocyclic phosphenium cations, the tendency to chemically and thermally eliminate carbodiimide, and the scarcely observed ring expansion by insertion of a chloro(imino)phosphine into a P-N bond of the P-N-…

Effects of cimetidine, atropine and prostaglandin E2 on rat mucosal erosions produced by intragastric distension

1980

Abstract The effects of three typical antisecretory agents: cimetidine, atrophine and prostaglandin E2 were compared on an acute rat gastric ulcer model which consisted of perfusing the stomach continuously, at a high intraluminal pressure (120 mm H2O), with a simulated gastric juice (0.1 M HCl plus 600 mg pepsin/1). As the acid and pepsin are given exogenously the inhibitory action of the antisecretory drugs is obviated in this model. Cimetidine and atropine failed to reduce gastric erosions, whereas prostaglandin E2 markedly reduced the severity of the mucosal lesions with respect to control values. Long-term treatment with cimetidine also failed to increase the resistance of the gastric …

Tumour-derived and host-derived nitric oxide differentially regulate breast carcinoma metastasis to the lungs.

2004

To study the role of nitric oxide (NO) in lung metastasis of breast carcinoma, we isolated two cell clones (H and J) from the parental EMT-6 murine breast carcinoma cell line, based on their differential NO production. In vitro, EMT-6 J cells, but not EMT-6H cells, constitutively expressed inducible NO synthase (NOS II) and secreted high levels of NO. IL-1beta increased NO production in both clones, and TNF-alpha had a synergistic effect on IL-1beta-induced NO production, but NO production by EMT-6 J cells was always higher than by EMT-6H cells. Proliferation, survival and adhesion to lung-derived endothelial cells of both clones were similar and were not affected by NO. In vivo, both clone…