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Biomedical subjects

D Vedaldi

Publications and source records attributed to D Vedaldi.

At least 73 records · Page 4Linked to original sources
PubMed1978

Studies on the mechanism of action of mitomycin C.

The in vitro formation and properties of the molecular complex between mitomycin C and native DNA were examined by means of various experimental methods; the data obtained indicate that the complex is extremely weak and that the chromophoric moiety of the antibiotic is not involved in its formation. The alkylating activity of mitomycin C was also studied using 3H-mitomycin C; while monofunctional alkylation increases almost in parallel with the concentration of the antibiotic, the difunctional alkylation, causing inter-strand cross-linkages in DNA, rapidly reaches a maximum and then remains constant even when increasing the concentration of the antibiotic and monofunctional alkylation. On the basis of these results, the currently accepted molecular model of the mitomycin--DNA interaction must be revised; a new model of this interaction is presented, which is in better agreement with the properties of mitomycin C and with the latest findings on the subject.

Alkylation↗
PubMed1977

DNA receptor sites for the intercalation of nogalamycin.

The intercalation of the planar chromophoric moiety of nogalamycin between two base pairs of duplex DNA has been evidenced by means of low-dichroism measurements. The possible presence of specific binding sites for mogalamycin on DNA has been suggested by studies on the denaturation and renaturation of DNA complexed with nogalamycin. A clear evidence was obtained by investigating the interaction of nogalamycin with polydeoxyribonucleotides containing known, regularly repeating sequences, used as model compounds. The results obtained with these polymers and the DNA suggest that the segment containing both purine (A,G) anf pyrimidine (T,C) bases in alternate sequences is the preferential receptor site on the DNA. A decreasing affinity is exhibited by poly d(A--T)-poly d(A--T), poly d(G--C)-poly d(G--C) and poly dG-poly dC segments, in the order. The poly dA-poly dT sequence appears to be closed to the interaction of nogalamycin.

Animals↗
PubMed1976

Receptor sites of DNA for the photoreaction with psoralen.

Biological and pharmacological effects of psoralens are correlated to their capacity to photoreact with pyrimidine bases of native DNA and in particular to form inter-strand cross-linkages. To determine possible prefenrential sites for the photoreaction the Authors have studied the capacity of psoralen to form complexes and to photoreact with various polynucleotides. The Authors have shown that specific sites exist in DNA for the photochemical interaction with psoralen; these sequences which can be considered as specific receptors for photobiological activity of psoralen are represented by alternate sequences in every strand of A and T, corresponding to poly d(A--T) - poly d(A--T). These receptor sites show a high capacity for intercalation and successive photoreaction with psoralen.

Animals↗
PubMed1975

Antimicrobial properties of some 3-acyl-4,7-disubstituted indoles.

In continuation of research on indole derivatives as potential chemotherapeutic agents, the antimicrobial properties of some 4,7-disubstituted 3-acylindoles were studied; the derivatives tested were 4,7-dimethoxy-, 4-hydroxy-7-methoxy-, 4,7-dihydroxyindoles and indole 4,7-quinones. Only the dihydroxy compounds (V a-c) proved active against certain bacterial strains. In order to test whether the action mechanism was analogous to that of mitomycin, a series of experiments was carried out to study the formation of complexes with DNA. It was found that only the substances with antimicrobial activity can form complexes, and it is therefore suggested that the action mechanism involves interference with cellular DNA.

Bacteria↗
PubMedDate not supplied

Photosensitized effects of furocoumarins: the possible role of singlet oxygen.

The capacity of various furocoumarins to generate singlet oxygen in aqueous solution has been determined. The antiproliferative and the skin-photosensitizing activities of the same furocoumarins did not show any correlation with the capacity to generate the singlet oxygen, while these photobiological properties could be correlated with the capacity of furocoumarins to induce photolesions to the DNA.

Animals↗
PubMedDate not supplied

Inhibition of cAMP phosphodiesterase by some phototherapeutic agents.

The behaviour of cyclic-3',5'-AMP phosphodiesterase has been studied in the presence of psoralen, 8-methoxy-psoralen (8-MOP), 4,5',8-trimethylpsoralen (TMP) (usually used in PUVA therapy), 4,6,4'-trimethylangelicin (TMA) and khellin recently proposed for the same therapeutical use. TMP and TMA exhibit a significant inhibitory effect on cyclic AMP phosphodiesterase; a light inhibition is produced by khellin at rather high concentration.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMedDate not supplied

Dark and photohemolysis of erythrocytes by furocoumarins.

It has been shown that various furocoumarins are able to cause dark hemolysis in red blood cells (RBC). However, this effect is evident only at relatively high furocoumarin concentrations (4.6 x 10(-4) M) - much higher than those used in photosensitization experiments or photochemotherapeutic treatments. Among the various furocoumarins examined in this study, only psoralen (Ps) and 3-carbethoxypsoralen (3-CPs) showed strong photohemolytic effects, while the other compounds revealed little or no activity. This fact indicates that Ps and 3-CPs are able to induce selective damage to the cell membrane of RBC. By pre-irradiating furocoumarin in ethanol or isotonic saline solutions and adding the irradiated solutions to a RBC suspension, hemolysis was observed in various compounds. The products of photolysis which form during pre-irradiation may be responsible, in terms of hemolysis, for toxic effects on RBC.

Darkness↗