Disease relevance of MDL72527

• The possible effects of the polyamine interconversion pathway on tissue polyamine levels, brain edema formation, and ischemic injury volume were studied by using a selective irreversible inhibitor, MDL 72527, of the interconversion pathway enzyme, polyamine oxidase [1].
• Previously we have shown that the specific polyamine oxidase (PAO) inhibitor N1,N4-bis(2,3-butadienyl)-1,4-butanediamine (MDL 72527) reduced the tissue putrescine levels, edema, and infarct volume after transient focal cerebral ischemia in spontaneously hypertensive rats and traumatic brain injury of Sprague-Dawley rats [2].
• Effect of the polyamine oxidase inactivator MDL 72527 on N(1)-(n-octanesulfonyl)spermine toxicity [3].
• An almost complete prevention of tumor growth was achieved in U-251 human glioblastoma xenografted nude mice, by partial decontamination of the gastrointestinal tract and feeding of a polyamine-free diet containing inhibitors of ornithine decarboxylase (DFMO) and of polyamine oxidase (MDL 72527) [4].
• Toxicity of enzymatic oxidation products of spermine to human melanoma cells (M14): Sensitization by heat and MDL 72527 [5].

High impact information on MDL72527

• Inhibition of PAO1 by MDL 72527 or by PAO1 small interfering RNA significantly attenuated H. pylori-induced apoptosis [6].
• Effects of MDL 72527, a specific inhibitor of polyamine oxidase, on brain edema, ischemic injury volume, and tissue polyamine levels in rats after temporary middle cerebral artery occlusion [1].
• In an intraluminal suture occlusion model of middle cerebral artery in spontaneously hypertensive rats, 100 mg/kg MDL 72527 changed the brain edema formation from 85.7 +/- 0.3 to 84.5 +/- 0.9% in cortex (p < 0.05) and from 79.9 +/- 1.7 to 78.4 +/- 2.0% in subcortex (difference not significant) [1].
• Polyamine depletion was achieved by inhibition of ornithine decarboxylase using 2-(difluoromethyl)ornithine, limitation of exogenous polyamines by administration of a polyamine-poor diet and decontamination of the gastrointestinal tract, and inhibition of endogenous polyamine reutilization by N,N'-bis-(2,3-butadienyl)putrescine (MDL 72527) [7].
• After 10 weeks of carcinogen treatment, one-half of the animals in each group were also concomitantly given i.p. injections of MDL 72527 (20 mg/kg body wt/week), a specific inhibitor of polyamine oxidase, until they were killed [8].

Chemical compound and disease context of MDL72527

• In contrast, toxicity of trifluoperazine, a calmodulin antagonist with a polyamine-unrelated structure, was not enhanced by MDL 72527 [3].

Biological context of MDL72527

• In addition, in view of recent studies that have indicated that polyamines may influence certain oncogenes in human colonic carcinoma cells, tumors from DMH +/- MDL 72527 were analyzed for K-ras mutations [8].
• N1,N4-di-n-butyl-1,4-butanediamine proved to be a cytotoxic agent of considerable potency, which induces mainly non-apoptotic cell death, whereas MDL 72527 causes under identical conditions both, apoptotic and non-apoptotic cell death [9].
• At 150 micromol/L MDL 72527, SW620 cells accumulated in S-phase of the cell cycle, showed decreased polyamine transport rate, and showed no increase of polyamine N1-acetyltransferase activity [10].

Anatomical context of MDL72527

• Exposure of the cells to MDL 72527, a compound considered to be a selective inactivator of polyamine oxidase (PAO) increased the cytotoxicity of N(1)OSSpm to both cell lines [3].
• The increase in putrescine levels in both the traumatized and nontraumatized cortex and hippocampus was reduced by a mean of 60% with MDL 72527 treatment [11].
• MDL 72527 (at 300 muM) produced in M14 cells numerous cytoplasmic vacuoles which, however, disappeared by 24 h, even in the presence of the drug [5].

Associations of MDL72527 with other chemical compounds

• Therefore we presume that the enhanced procyanidin-triggered apoptosis by MDL 72527 is mediated by the accumulation of N(1)-acetyl-polyamines [12].
• In contrast, MDL 72527 did not change the apoptosis rate and the N1-acetylspermidine content in cells treated with 7beta-OHsitosterol [13].
• Systemic injection of kainic acid in adult rat is accompanied by a large increase in the accumulation of acetylated derivatives of spermidine and spermine in the hippocampus and piriform cortex of animals pretreated with the polyamine oxidase inhibitor, MDL 72527 [14].
• RESULTS: Lysosomotropic drugs (MDL 72527, phenylalanine methylester and chloroquine) amplified procyanidin-induced growth inhibition and apoptosis in SW620 cells at non-cytotoxic concentrations [15].
• N1,N4-bis(2,3-butadienyl)-1,4-butanediamine (MDL 72527) was considered to be a selective inactivator of FAD-dependent tissue polyamine oxidase [10].

Gene context of MDL72527

• Potentiation of apple procyanidin-triggered apoptosis by the polyamine oxidase inactivator MDL 72527 in human colon cancer-derived metastatic cells [12].
• The observation that apple procyanidins enhance polyamine catabolism and reduce polyamine biosynthesis activity similar to known inducers of SSAT, without sharing their toxicity, and the potentiation of these effects by low concentrations of MDL 72527 suggests apple procyanidins for chemopreventive and therapeutic interventions [12].
• Some biochemical modification of MDL 28302 and MDL 29431 appeared to be required for their inhibitory activities to be exerted, since the effects of these drugs on T. cruzi infectivity were abrogated by MDL 72527, a drug known to inhibit polyamine oxidase (PAO) activity specifically [16].
• The polyamine oxidase inactivator MDL 72527 [17].
• Interaction of bovine serum amine oxidase with the polyamine oxidase inactivator MDL 72527 [18].

References