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Biomedical subjects

F Bordin

Publications and source records attributed to F Bordin.

At least 73 records · Page 4Linked to original sources
PubMed1981

Photochemotherapy of skin-diseases: comparative studies on the photochemical and photobiological properties of various mono- and bifunctional agents.

The antiproliferative activity of the classic photochemotherapeutic agents, that is bifunctional psoralens (8-methoxypsoralen, 8-MOP; 5-methoxypsoralen, 5-MOP; 4,5',8-trimethylpsoralen, TMP) as well as of those more recently proposed, that is, monofunctional furocoumarins (methylangelicins and 3-carbethoxypsoralen, 3-CPs) is ascribed to their capacity to photo-induce lesions in DNA. In this connection while bifunctional agents photo-induce both mono- and bifunctional (inter-strand cross-linkages) damages in the macromolecule both in vitro and in vivo, monofunctional furocoumarins photodamage DNA only through monofunctional lesions. To have a direct and precise comparison between the classic agents (8-MOP, 5-MOP, TMP) and those recently proposed (4,5'-dimethylangelicin, 4,5'-DMA; 3-CPs), we have made a comparative study of the capacity of the various compounds to form the dark complex with DNA as well as of their capacity to induce mono- and bifunctional damages in the macromolecule. A comparative study on the antiproliferative activity in terms of capacity to inhibit DNA and RNA synthesis in Ehrlich ascites tumor cells as well as of the capacity to inhibit epidermal DNA synthesis in mice is also reported. The emerging picture can give a precise comparison in terms of both photobinding to DNA, as well as antiproliferative and skin-phototoxic activities between the classic agents 8-MOP, 5-MOP, TMP and the new monofunctional agents 4,5'-DMA and 3-CPs.

Chemical Phenomena↗
PubMed1981

A new water soluble derivative of 4,5'-dimethylangelicin as a potential agent for photochemotherapy.

A water soluble derivative of 4,5'-dimethylangelicin (I) having a long chain linking an amino group to the planar furocoumarinic moiety, that is 4'-N,N-dimethylaminoethoxymethyl-4,5'-dimethylangelicin (III), has been prepared. This compound is able to form effectively the intercalated complex with DNA like the previously prepared 4'-aminomethyl-4,5'-dimethylangelicin (II), however while the compound (II) showed very poor photobinding to DNA, the new derivative (III) shows high photobinding to the macromolecule. It is proposed that these data illustrate the importance of the geometry of intercalation for the subsequent covalent photobinding to the macromolecule. Also some photophysical data of (II) and of (III) appear to confirm the critical role of the position assumed by the chromophore of the two compounds when intercalated in duplex DNA. The compound (III) displays high photobiological effects, also in terms of antiproliferative activity as shown by its capacity to inhibit DNA and RNA synthesis in Ehrlich cells, the growth of an E. coli culture and the infectivity of T2 phage. (III) on the basis of these properties seems to deserve a clinical evaluation of its potential photochemotherapeutic activity in the treatment of psoriasis.

Animals↗
PubMed1981

Carbomethoxy-derivatives of psoralen: interactions with DNA and photobiological properties.

The dark and photochemical interactions with DNA in vitro as well as the photobiological properties of two psoralen derivatives having a carbomethoxy-group inserted in 3 or 5' position of the furocoumarin nucleus were studied. 3-Carbomethoxy-4',8-dimethylpsoralen photoreacts with DNA in vitro to a very small extent and, as a consequence, it appears to be photobiologically ineffective. On the contrary, 5'-carbomethoxy-4,8-dimethylpsoralen appears very interesting, showing a photobinding and cross-linking capacity with DNA in vitro higher than that of 8-MOP. A similarly higher photobiological activity was also demonstrated, with respect to this reference compound, in experiments on inhibition of DNA and RNA synthesis in Ehrlich ascites tumor cells, and on the killing of bacteria and of T2 bacteriophage. Finally, this compound inhibited the tumor transmitting capacity of Ehrlich ascites tumor cells.

Animals↗
PubMed1981

Photochemical and photobiological properties of 4,5'-dimethylpsoralen, a bifunctional contaminant of synthetic 4,5'-dimethylangelicin.

4,5'-Dimethylpsoralen, a bifunctional furocoumarin, can be formed as an impurity in the synthesis of its angular isomer, that is 4,5'-dimethylangelicin; the latter has recently been proposed as a potential monofunctional agent for photochemotherapy. To have precise information on the possible modifications of the photochemical and photobiological properties of synthetic 4,5'-dimethylangelicin caused by the presence of its linear isomer, we have studied the interactions of the latter with DNA in both the ground and the excited state and its photobiological activity. 4,5'-Dimethylpsoralen photobinds much more effectively to DNA than its angular isomer and is capable to form effectively inter-strand cross-linkages in DNA while dimethylangelicin is unable to form these bifunctional adducts in DNA. Dimethylpsoralen shows a strong skin-phototoxicity while angelicin lacks this activity. Moreover the antiproliferative activity of the psoralen derivative in terms of DNA synthesis inhibition in Ehrlich cells and of inhibition of infectivity of T2 phages, is about four times higher than that of the angular isomer. These data stress the necessity of the absence of the isomeric linear furocoumarin in the synthetic 4,5'-dimethylangelicin because its presence can markedly modify the photobiological and phototherapeutic properties of the angelicin derivative.

Animals↗
PubMed1980

Comparative mutagenicity of linear and angular furocoumarins in Escherichia coli strains deficient in known repair functions.

Four furocoumarins, two having a linear molecule, psoralen and 8-methyl-psoralen and two having an angular molecule, angelicin and 4,5'-dimethyl-angelicin were tested for mutagenesis in Escherichia coli B wild type and in various strains deficient in known repair systems. The results indicate that both monoadducts and crosslinks are mutagenic. The mutagenic efficiency of the furocourmarins ranks in the following order 8-methylpsoralen psoralen greater than angelicin greater than 4,5'-dimethylangelicin.

DNA Repair↗
PubMed1980

Antiviral activity of some congeners of tilorone.

The activity of four tilorone analogous compounds against three different strains of E. coli bacteriophages T1, T2 and phiX-174, was studied. Among the compounds we tested, only a fluorene derivative (2,7-bis-2-[2-(diethylamino)acetyl]fluorene) yielded a high inhibition of phage growth, to a greater extent with respect to tilorone, used as a reference compound. This activity, not due to a toxic effect on the host bacteria, did not appear connected with a complex formation between the drug and DNA. In fact, among the studied compounds, this is not the one showing the highest binding parameters with DNA; in addition, when the mature virions were incubated in the presence of the drug and then diluted and assayed for their plaque-forming capacity, this drug turned out to be practically ineffective. Fluorene derivative appears to be an antiviral drug acting on an unidentified metabolic process of phage growth, and therefore it is a model for new antiviral drugs showing a selective activity.

Antiviral Agents↗
PubMed1979

lambda-Prophage induction by furocoumarin photosensitization.

Furocoumarin photosensitization induces lambda-prophage from lysogenic Escherichia coli cells; this effect is clearly due to the photoreaction that furocoumarins give with DNA, and it appears connected with the formation of monoadducts rather than of diadducts (cross-links).

Coliphages↗
PubMed1979

Diethylaminoalkyloxycoumarin and -furocoumarin derivatives.

Four series of diethylaminoalkoxyderivatives of coumarin (at the positions 4 and 7) and furocoumarin (at the positions 5 and 8) have been prepared, in order to study their complexing capacity with DNA, these compounds having a double possibility of interaction, that is intercalation of the aromatic moiety between two base pairs and formation of an electrostatic bond between their terminal amino group and a phosphoric group of DNA. Some biological effects connected with the interaction with DNA have also been studied. The results obtained showed that coumarin derivatives have a low complexing capacity and lack any biological activity. The furocoumarin derivatives showed a markedly increased complexing capacity both in respect to the coumarin derivatives and to the parent furocoumarin (psoralen, as well as its 5- and 8-methoxy derivatives) and proved able to inhibit DNA and RNA synthesis in Ehrlich ascites tumor cells, as well as the growth of Staphylococcus aureus and of various strains of Escherichia coli. This activity was generally low but was constantly higher in 5-than in 8-derivatives, the same behavior being found with regard to the complexing capacity with DNA. A good correlation between the ability to form complexes with DNA and the capacity to inhibit cells growth was clearly evidenced.

Animals↗
PubMed1979

New studies on the interaction between 8-methoxypsoralen and DNA in vitro.

Some aspects of the interactions between DNA and 8-methoxypsoralen (8-MOP) in its ground state (complex formation) or in its excited state (photobinding) have been investigated. 8-MOP shows a low affinity towards DNA in the complex formation; this fact minimizes the possible biological consequences deriving from this interaction, when it occurs in vivo. In covalent photobinding to DNA, 8-MOP forms mainly monofunctional adducts, and to a lesser extent bifunctional adducts, showing a behavior similar to that of other linearly condensed furocoumarins (psoralens); the ratio between mono- and bifunctional adducts was found to be 9:1. The covalent photobinding to DNA does not occur at random along the macromolecule, but preferentially at the level of specific receptor sites. The regions having an alternate sequence of A-T seem to be the best receptor sites for the formation of monoadducts while the regions containing an alternate sequence of A-T and C-G appeared to be the preferential sites for the cross-linkage formation.

Base Sequence↗
PubMed1979

Interaction between DNA and some congeners of tilorone.

Four compounds having a molecular structure analogous to that of tilorone and tilorone itself, taken as a reference compound, were examined for complex formation ability with DNA. While the association constants of the various complexes were almost the same, the r values in saturation conditions (that is the highest number of molecules bound per nucleotide of DNA) increased with the size of the planar moiety or with the length of the two basic side chains of the molecules. Concerning the structure of the complexes, it was evidenced by means of flow dichroism measurements that the non-covalent binding to DNA occurs via an intercalative mode. Moreover, it was observed that by decreasing the ionic strength, the affinity of the drugs for the macromolecule increases, indicating that in complex formation, electrostatic forces exerted between the DNA phosphate residues and the positively charged nitrogen of the side chains of the drugs are involved. It seems also possible that, in this condition, and in the presence of high concentrations of the drug, a secondary binding consisting only of electrostatic interactions outside of the helix takes place. In connection with the complexing ability with DNA, the examined compounds proved able to inhibit DNA and RNA synthesis in Ehrlich ascites tumor cells. A correlation was found between complexing ability and inhibitory activity on nucleic acid synthesis.

Animals↗
PubMed1976

DNA repair and recovery in Escherichia coli after psoralen and angelicin photosensitization.

The correlation between DNA repair and recovery of biological functions was studied using three wild type strains of Escherichia coli and two skinphotosensitizing furocoumarins, psoralen and angelicin, which are well known specific reagents of the pyrimidine bases of DNA. In addition to mono-adducts psoralen is able to form a high number of inter-strand cross-links, while angelicin forms only mono-adducts. Both of these damages were repaired, in a short time, in the following way: at first DNA was cut into small pieces that were then rejoined into molecules of normal size, free from cross-links, while the furocoumarin residue was split from DNA almost quantitatively. Recovery of biological functions was studied performing photosensitization experiments in such a manner that the same amounts of psoralen or of angelicin were linked to bacterial DNA. DNA synthesis, tested just after the damage, was inhibited in a similar extent by both drugs. The same bacteria, however, showed a very different colony-forming capacity; angelicin was much less effective than psoralen with a D37 dose about 2.7 times higher. A similar picture was obtained studying DNA synthesis at different times after photosensitization: in the bacteria damaged by angelicin it was restored while no recovery was observed in cells photosensitized by psoralen. These results suggest that both mono-adducts and cross-links can be chemically repaired more or less in a quantitative measure, but that repair of cross-links in much less effective on cell recovery; this behaviour is very probably connected with the different repair mechanisms of mono-adducts and of cross-links.

Coumarins↗