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Diego Monti

Publications and source records attributed to Diego Monti.

9 recordsLinked to original sources
PubMed2005

Major artifacts encountered in studying biological samples containing ferric protoporphyrin IX.

Heme (ferric protoporphyrin IX, FP) dissolves very rapidly into the lipid phase of membranes, and a large number of studies have focused attention on its possible toxic effect in whole cells or isolated membranes. However, because of its molecular structure and reactivity, different problems can be encountered during the course of studying biological samples containing FP. In this article, we discuss important interferences by FP and artifacts that can affect the experimental values. First, FP interferes with the Lowry's protein determination; therefore, membranes containing FP are overestimated in their protein content determined by this procedure. Second, freezing membranes at -20 degrees C artifactually increases the local concentration of FP, thereby enhancing FP-induced lipid peroxidation. Third, in the presence of thiol compounds such as N-acetyl cysteine, FP is degraded to products that interfere with the thiobarbituric acid assay, one of the most widely used methods to measure the extent of lipoperoxidation.

Acetylcysteine↗
PubMed2004

Differential activation of heme oxygenase-1 by chalcones and rosolic acid in endothelial cells.

The induction of heme oxygenase-1 (HO-1) is widely recognized as an effective cellular strategy to counteract a variety of stressful events. We have shown that curcumin and caffeic acid phenethyl ester, two naturally occurring phytochemicals that possess antioxidant, anti-inflammatory, and anticarcinogenic activities, induce HO-1 in many cell types. This suggests that stimulation of HO-1 could partly underlie the beneficial effects exerted by these plant-derived constituents. Here we examined the ability of additional plant constituents to up-regulate heme oxygenase activity and HO-1 in aortic endothelial cells. Incubation of endothelial cells with a series of polyphenolic chalcones (5-50 microM) resulted in increased heme oxygenase activity; interestingly, the chemical structure dictated the pattern of heme oxygenase induction, which was unique to each particular compound employed. We also found that rosolic acid, a constituent isolated from the rhizome of Plantago asiatica L. dramatically increased HO-1 in a concentration- and time-dependent manner. Severe cytotoxicity was observed after prolonged exposure (24 or 48 h) of cells to curcumin and caffeic acid phenethyl ester, whereas 2'-hydroxychalcone and rosolic acid did not affect cell viability. By using different mitogen-activated protein kinase inhibitors, we determined that the extracellular signal-regulated kinase, p38, and c-Jun NH(2)-terminal protein kinase pathways play only a minor role in the induction of HO-1 by rosolic acid and 2'-hydroxychalcone. On the other hand, increased intra- and extracellular thiols markedly reduced the rise in heme oxygenase activity elicited by rosolic acid. Thus, this study identified novel plant constituents that highly induce HO-1 in endothelial cells and investigated some of the mechanisms involved in this effect.

Animals↗
PubMed2004

Evidence that haem iron in the malaria parasite is not needed for the antimalarial effects of artemisinin.

The role of haem iron (II) and oxidative stress in the activation and antimalarial activity of artemisinin is unclear. Thus, we submitted malaria parasite to modified culture conditions: artemisinin activity increased by 20-30% under an oxygen-rich atmosphere (20% O2 instead of "standard" 1% O2), and by 40-50% in the presence of carboxy-haemoglobin, and 2% carbon monoxide, conditions which inhibit haem iron (II) reactivity. In all cases, parasite growth and chloroquine activity were unaffected. We conclude that in the malaria parasite artemisinin is not activated by haem iron and that free radicals are not needed for its toxicity.

Animals↗
PubMed2003

New approach for the detection of BSH and its metabolites using capillary electrophoresis and electrospray ionization mass spectrometry.

Boron neutron capture therapy is a promising binary treatment for cancer. It is based on the nuclear fission that occurs when non-radioactive 10B absorbs thermal neutrons. One of the two boron compounds currently used in clinical trials for this therapy is BSH. To ensure differentiated retention in the tumour versus normal tissue prior to treatment, routine analytical methods to determine pharmacokinetics must be available. For this purpose we have developed a new, easy and time saving approach, in which the separation of boron derivatives is performed by means of capillary electrophoresis (CE). The CE method allows analyses to be performed in short times (less than 18 min), sensitively (LOD 8 pg loaded on the capillary) quantitatively (LOQ 5 microg/ml) and with a high efficiency of separation. Moreover it is simpler than HPLC and more reproducible (intra- and inter-day values were +/-1% and +/-3%, respectively), and does not require a specific column of derivatization. Mass spectrometry analysis of boron derivatives in different samples was also performed to ensure correct attribution of the CE peaks.

Boron Compounds↗
PubMed2003

Mimics of ganglioside GM1 as cholera toxin ligands: replacement of the GalNAc residue.

Two new cholera toxin (CT) ligands (4 and 5) are described. The new ligands were designed starting from the known GM1 mimics 2 and 3 by replacement of their GalNAc residue with the C4 isomer GlcNAc. As predicted by molecular modelling, the conformational properties of the equivalent pairs 2-4 and 3-5 are very similar and their affinity for CT is of the same order of magnitude. NMR experiments have also proved that 5 occupies the GM1-binding site of the toxin and have revealed its bound conformation.

Acetylgalactosamine↗
PubMed2002

Structure-activity relationships in 4-aminoquinoline antiplasmodials. The role of the group at the 7-position.

Antiplasmodial activities versus the chloroquine sensitive D10 strain of Plasmodium falciparum of a series of N(1),N(1)-diethyl-N(2)-(4-quinolinyl)-1,2-ethanediamines with 11 different substituents at the 7-position on the quinoline ring have been investigated in vitro. Electron-withdrawing groups at the 7-position have been shown to lower the pK(a) of both the quinoline ring nitrogen atom and the tertiary amino nitrogen in the alkyl side chain. The quinoline nitrogen pK(a) ranges from 6.28 in the nitro derivative to 8.36 in the amino derivative, while the tertiary amino nitrogen has a pK(a) ranging between 7.65 in the trifluoromethyl derivative and 10.02 in the amino derivative. Calculation suggests that the resulting pH trapping of these compounds in the parasite food vacuole ranges between about 7% of that observed in chloroquine for the NO(2) derivative and 97% in the amino derivative. A direct proportionality between antiplasmodial activity normalized for pH trapping and beta-hematin inhibitory activity was observed. Activity could not be correlated with any other observed physical parameter. The beta-hematin inhibitory activity of these derivatives appears to correlate with both the hematin-quinoline association constant and the electron-withdrawing capacity of the group at the 7-position (Hammett constant). For the compounds under investigation, the hematin association constant is in turn influenced by the lipophilicity of the group at the 7-position.

Aminoquinolines↗
PubMed2002

Does chloroquine really act through oxidative stress?

To assess whether molecular oxygen and oxidative stress contribute to chloroquine activity, we cultivated strains of Plasmodium falciparum in erythrocytes with carboxyhemoglobin and an atmosphere containing 2% CO, 5% CO(2) and 93% N(2). Results indicate that, contrary to common belief, oxygen is not involved in the activity of chloroquine. Reactive radicals formation is suggested.

Animals↗
PubMed2002

Synthesis and structural characterization of the [[Rh(5)(CO)(14)]-(H(2)N(CH(2))(4)NH(2))-[Rh(5)(CO)(14)])](2-) and [Rh(5)(CO)(13)(H(2)N(CH(2))(2)NH(2))](-) anions (as [PPh(4)](+) salts): an unprecedented example of carbonyl substitution by alkylamines in a homoleptic metal carbonyl cluster anion.

The substitution of one or two carbonyls by many different primary and secondary alkylamines and -diamines has been established for the first time in a homoleptic carbonyl cluster anion, the trigonal bipyramidal [Rh(5)(CO)(15)](-). Two derivatives, the bis-monosubstituted [[Rh(5)(CO)(14)]-(H(2)N(CH(2))(4)NH(2))-[Rh(5)(CO)(14)]](2-) dianion (1) and the disubstituted chelated [Rh(5)(CO)(13)(H(2)N(CH(2))(2)NH(2))](-) monoanion (2), have been structurally characterized, both in the solid state (as [PPh(4)](+) salts) and in solution, revealing that the sites of the substitution are the cluster apexes. (13)C NMR spectra of 2 revealed localized fluxionality of the CO ligands over the temperature range 298-183 K.

Journal Article↗