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Biomedical subjects

F Baccichetti

Publications and source records attributed to F Baccichetti.

At least 55 records · Page 3Linked to original sources
PubMed1989

1H-pyrrolo[2,3-f]quinoline and isoquinoline derivatives: synthesis and antiproliferative activity.

Fischer indol synthesis is reported for the preparation of some 2-substituted 1H-pyrrolo[2,3-f]quinoline and isoquinoline derivatives having a structural correlation with naturally occurring compound ellipticine. The prepared compounds proved capable of forming in vitro molecular complexes with native double-stranded DNA by intercalation between two base pairs and showed a relatively good activity in inhibiting the DNA synthesis in Ehrlich ascites tumor cells.

Animals↗
PubMed1988

Synthesis and photobiological activity of new N,N-disubstituted 4-amino-3-chloroangelicins.

The synthesis of a series of new N,N-disubstituted 4-amino-3-chloroangelicins (4-amino-3-chloro-2H-furo[2,3-h]-1-benzopyran-2-ones) starting from N,N-disubstituted (E)-5-aminomethylene-6,7-dihydrobenzo[b]furan-4(5H)-ones is described. Their capacity of inhibiting DNA synthesis in Ehrlich ascites tumor cells by U.V.-A light irradiation as well as their phototoxic activity on guinea-pig skin have been studied and the data computed by probit analysis; the results are discussed in the light of the modifications introduced in the molecular structure.

Animals↗
PubMed1987

Photochemical, photophysical and photobiological properties of some methylallopsoralens which are potential agents for photochemotherapy.

Two new trimethylallopsoralens, 4,7,4'- and 4,7,5'-trimethylallopsoralen, form molecular complexes with DNA and by successive UVA (320-400 nm) irradiation photobind monofunctionally to the macromolecule. The DNA photobinding rates at 365 nm and photobinding quantum yields at 330 nm are markedly higher for 4,7,4'-trimethylallopsoralen than for 4,7,5'-trimethylallopsoralen. Their capacities to generate singlet oxygen in water and benzene are low, particularly for 4,7,4'-trimethylallopsoralen, and the two trimethylallopsoralens completely lack skin phototoxicity on guinea-pig skin. Both compounds show antiproliferative activity in terms of DNA synthesis inhibition in Ehrlich cells and T2 phage infectivity higher than that displayed by angelicin. In view of its monofunctional character, lack of skin phototoxicity, low singlet oxygen yield and antiproliferative activity, 4,7,4'-trimethylallopsoralen deserves further clinical studies as a potential photochemotherapeutic agent.

Benzene↗
PubMed1986

Photobiological activity of certain pyranocoumarin derivatives: potential agents for the photochemotherapy of psoriasis.

The photobiological properties of a series of pyranocoumarin derivatives having linear (xanthyletines) and angular structure (seselins) have been studied; while the linear derivative carrying the methyl geminal group, typical of the parent natural compound, appeared to be entirely inactive in all tests performed, very probably because of the steric hindrance in the dark interaction with DNA, 4 substances lacking in this group showed a marked capacity for inhibiting DNA synthesis in Ehrlich cells. In particular, 4,6-dimethyl-8-desmethylseselin proved to be about 7 times more active than 8-MOP. Practically all compounds were capable of inducing cross-links in DNA, but this feature, marked in the linear compounds, is very much reduced in the angular ones; this property appears to be clearly related to the mutagenicity in the light and with the skin phototoxicity, which are both marked in the former and low or absent in the latter. In the dark, while all compounds are non-mutagenic in the absence of metabolic activation, in the presence of microsomial enzymes pyranocoumarins become mutagens; only the xanthyletine derivative carrying a geminal methyl group at the 8 position was not activated, suggesting that the enzymes metabolize the pyranic ring.

Animals↗
PubMed1986

N,N-disubstituted 4-amino-3-chloroangelicins: interactions with DNA in the ground and in the excited states (365 nm).

The interactions between three N,N-disubstituted 4-amino-3-chloroangelicins and DNA in the ground and in the excited states have been examined. The three compounds form a molecular complex with DNA in the dark, but to a quite different extent. Spectrophotometric and fluorimetric data suggest that while 3-chloro-4-dimethylaminoangelicin (III) undergoes intercalation between two phase pairs of DNA, the compounds i.e. 3-chloro-4-methylphenyl amino angelicin (I) and its 5,6-dihydroderivative (II) should not undergo intercalation. Compound (I) photobinds to DNA to an extent similar to that of parent angelicin, while compound (III) photobinds to the macromolecule much more effectively. This fact may be attributed to the more suitable type of molecular complex (intercalation) formed by compound (III) with the macromolecular in respect to that formed by compound (I). The observed very low ability of compound (II) both to form a complex and to photobind with DNA can be ascribed primarily to the marked modification of the chromophore due to the saturation of the 5,6 double bond in the central benzene ring.

Chemical Phenomena↗
PubMed1984

6-Methylangelicins: a new series of potential photochemotherapeutic agents for the treatment of psoriasis.

The possible presence of methylpsoralens as undesired inquinants in synthetic methylangelicins has been avoided through a synthetic pathway starting from umbelliferones carrying a methyl group in the 6-position. The new 6-methylangelicins show a high affinity toward DNA, forming in the dark a molecular complex; the complexed angelicins under UV-A irradiation photobind effectively to the macromolecule, forming only monoadducts. The new compounds show an evident antiproliferative activity by inhibiting DNA synthesis on Ehrlich cells; great differences, however, can be seen between the various compounds. All the compounds are lacking of skin erythemogenic activity. Some of the new 6-methylangelicins, evaluated in terms of mutagenic activity, demonstrate to be less effective than 8-methoxypsoralen (8-MOP), used for a comparison. On the basis of antiproliferative activity, lack of skin phototoxicity, and low mutagenicity, two compounds have been chosen for clinical evaluation. The compounds tested on seven psoriatic patients by topical application and UV-A irradiation proved to be more effective than 8-MOP, used in the same conditions.

Animals↗
PubMed1984

Bis-pyridoquinolines as new bifunctional intercalators for DNA.

With the aim of obtaining new bifunctional intercalators for DNA, a new series of bis-pyridoquinolines were synthesized by joining two tricyclic planar moieties through a flexible chain. For preparing the corresponding potential monofunctional intercalators also a series of mono-pyridoquinolines were prepared by chemical synthesis by joining the same chromophore with a flexible side-chain. The melting profiles of the complexes between two bis-pyridoquinolines and DNA showed two different thermal transitions supporting the bis-intercalation of the ligand with the macromolecule. On the other hand, two mono-pyridoquinolines showed only one transition in the melting profile indicating a behaviour consistent with a mono-intercalation. The antiproliferative activity was tested in terms of DNA synthesis inhibition in Ehrlich ascite tumor cells; the examined bis-intercalating agent showed to be much more active than the tested mono-intercalating compound.

Aminoquinolines↗
PubMed1984

Synthesis and photobiological activity of N,N-disubstituted 4-amino-3-chloro-2H-thieno[2,3-h]-1-benzopyran-2-ones, 7-thioisosteres of 4-amino-3-chloroangelicins.

A convenient synthesis of a series of N,N-disubstituted 4-amino-3-chloro-2H-thieno[2,3-h]-1-benzopyran-2-ones (IV), which are 7-thioisosteres of 4-amino-3-chloroangelicins, was accomplished via dehydrochlorination and dehydrogenation of the 1,4-cycloadducts obtained by reaction of dichloroketene with N,N-disubstituted (E)-5-aminomethylene-6,7-dihydrobenzo-[b]thiophen-4(5H)-ones . Some aspects of the photobiological activity of these thioangelicins were studied; three of them (IV a, e, f) appeared to inhibit DNA synthesis in Ehrlich ascites tumor cells. The most active compound, namely 3-chloro-4-morpholino-7-thioangelicin (IV e), afforded 70% of the antiproliferative effect of 8-MOP, but unlike this reference compound was unable to induce erythema on guinea pig skin. However, compounds (IV a, f) produced a slight erythema, thus suggesting that a relationship between antiproliferative and phototoxic effects does not exist.

Animals↗
PubMed1983

4'-Methylangelicins: new potential agents for the photochemotherapy of psoriasis.

Three derivatives of angelicin (1) [4'-methyl-, 4,4'-dimethyl-, and 4',5-dimethylangelicin (2a-c)] have been prepared with the aim of obtaining new agents for the photochemotherapy of psoriasis. These compounds form a complex in the dark with DNA that shows an affinity for the macromolecule higher than that of the parent angelicin (1). A correlation between their octanol/water partition coefficients and the association constants of the complexes has been observed. Compounds 2a-c photobind to DNA to a much higher extent than 1 and also more effectively than 8-methoxypsoralen (8-MOP), taken as reference compound. When activated with UV-A, the three compounds strongly inactivate T2 phage and inhibit epidermal DNA synthesis in mice. Moreover, they show a mutagenic activity markedly lower than that of 8-methoxypsoralen on Escherichia coli wild-type strain. Due to its lack of skin phototoxicity, its low mutagenic activity, and its antiproliferative activity, 2c was chosen for clinical evaluation. It proved to be effective in clearing psoriasis in two patients.

Animals↗
PubMed1983

7-Methyl and 4,7-dimethylallopsoralen: monofunctional photoreagents toward DNA as potential photochemotherapeutic agents in hyperproliferative conditions.

7-Methyl- (1 a) and 4,7-dimethylallopsoralen (1 b), prepared about ten years ago and till now considered non-photosensitizing agents, have been re-investigated for studying their photochemical and photobiological properties. They form a molecular complex with DNA in the ground state, undergoing intercalation between two base pairs of the macromolecule. By successive irradiation with U.V.-A they covalently photobind to DNA inducing only the formation of mono-adducts. They are not able to induce erythema on guinea pig skin, but show evident antiproliferative activity on various biological substrates. Compound (1 b) shows both photochemical and photobiological properties at a degree higher than that of compound (1 a).

Animals↗
PubMed1983

Enzyme activities and metabolites along the kynurenine pathway in mice with Harding-Passey melanoma.

Tryptophan metabolism has been studied in mice with Harding-Passey melanoma and in controls, after a load of 1.0 g/kg b.w. of L-tryptophan by determining ten urinary metabolites of the kynurenine pathway and some enzyme activities involved in the degradation of this aminoacid. Kynurenine was the only tryptophan derivative excreted in significantly higher quantities in mice with melanoma with respect to the controls. This result is in agreement with a significantly higher activity of hepatic tryptophan pyrrolase in mice with melanoma. Liver kynureninase and liver and kidney kynurenine aminotransferase activities were similar in the two groups of mice. These findings point to a possible role of tryptophan in the biogenesis of melanins in pathological conditions such as in melanoma.

Animals↗
PubMed1981

Effect of blue light on the urinary excretion of tryptophan metabolites in adult heterozygous and homozygous Gunn rats.

Tryptophan metabolism along the kynurenine pathway has been studied in male and female heterozygous and homozygous adult Gunn rats after load of amino acid before and after exposure to blue light. The percentage of tryptophan metabolites in each group of rats was slightly higher in females than in males. Before irradiation the excretion of metabolites was larger in male and female heterozygous groups than the corresponding groups of the homozygotes. After irradiation only the groups of male and female heterozygous Gunn rats showed a decrease in the total excretion of the metabolites. Therefore blue light exposure dose not seem to influence the metabolism of tryptophan in homozygous Gunn rats.

Animals↗
PubMed1981

Enzyme activities of tryptophan metabolism in heterozygous and homozygous Gunn rats before and after blue light exposure.

The effect of light exposure in the enzyme activities, involved in the tryptophan metabolism along the kynurenine pathway, has been studied in male and female adult hetero-and homozygous Gunn rats. Light exposure did not seem to influence these enzyme activities. The groups of non-icteric heterozygotes however showed a higher activity of liver tryptophan pyrrolase than in the groups of icteric homozygotes. Kynureninase activity was similar in all the groups of rats, whereas liver kynurenine aminotransferase activity appeared slightly higher in the groups of male rats with respect to female rats, but no difference existed before and after irradiation. In addition the male heterozygotes showed a higher kynurenine aminotransferase activity in kidneys than the other groups of rats.

Animals↗
PubMed1981

Effect of psoralen-induced photodermatitis on tryptophan metabolism in rats.

Tryptophan metabolism 'via kynurenine' has been studied in rats before and after induction of experimental light-conditioned dermatitis with psoralen. Tryptophan load in animals during the acute phase of dermatitis (one day after induction) causes a markedly increased urinary excretion of total metabolites in comparison with that obtained before dermatitis. During this phase of the skin disease tryptophan pyrrolase activity is significantly increased and kynureninase activity significantly decreased in liver in respect to the control animals. Kynurenine aminotransferase activity shows no significant variations in both liver and kidneys. After 6 days of dermatitis, when the skin damage is in repair, both the excretory values of the urinary metabolites after L-tryptophan load and the enzymic activities are similar to those before dermatitis.

Animals↗
PubMed1981

New monofunctional reagents for DNA as possible agents for the photochemotherapy of psoriasis: derivatives of 4,5'-dimethylangelicin.

With the aim of obtaining new agents for the photochemotherapy of psoriasis, we have prepared monofunctional reagents for DNA by starting from 4,5'-dimethylangelicin (2), an angular furocoumarin, and introducing in a 4'-(hydroxymethyl) (3), 4'-(methoxymethyl) (4), or 4'-(aminomethyl) group (5), in way analogous to what other authors have done previously on trioxsalen, a DNA bifunctional reagent. These new compounds form complexes with DNA in the ground state and by successive irradiation (UV-A) undergo monofunctional photoaddition to the macromolecule. Photobinding to DNA was highest for 3 and gradually lower for 4 and 5, respectively. These compounds do not form interstrand photocross-linkages in DNA and do not show any skin phototoxicity. Fluorimetric studies show that their 4',5' double bond is involved in the photoaddition to DNA. Their photobiological activity evaluated on Ehrlich ascites tumor cells and on T2 phages was strictly connected with their photobinding to DNA. The effect of the introduction of hydroxymethyl and methoxymethyl groups in angular 2 is somewhat similar to that previously described for trioxsalen: the introduction of an aminomethyl group in 2 markedly increases the affinity in the dark for DNA but under UV-A irradiation strongly inhibits photobinding to the macromolecule. By contrast, in the analogous derivative of trioxsalen both the affinity for DNA in the dark and the photobinding to DNA increased.

Animals↗
PubMed1981

Methylangelicins: new potential agents for the photochemotherapy of psoriasis. Structure-activity study on the dark and photochemical interactions with DNA.

The interactions both in the ground and in the excited state between various methylangelicins, previously prepared with the aim to increase the low photobiological activity of the parent angelicin 1, and DNA have been studied. In general, the new methylangelicins show an increased capacity to photobind monofunctionally to DNA and a parallel increment of photobiological activity in comparison with the parent 1. This increase appears to be connected with various factors, such as the augmented affinity toward DNA for the dark complex formation and the electronic effect connected with the introduction into 1 of one or two methyl groups. The new compounds, on the basis of their photobiological activity and their lack of skin phototoxicity, appear as possible agents for the photochemistry of skin diseases characterized by cell hyperproliferation.

Chemical Phenomena↗