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Biomedical subjects

G Pratesi

Publications and source records attributed to G Pratesi.

At least 127 records · Page 7Linked to original sources
PubMed1981

Cross resistance and cellular uptake of 4'-O-methyldoxorubicin in experimental tumors with acquired resistance to doxorubicin.

A new analog of doxorubicin, 4'-O-methyldoxorubicin, was previously reported to have a pronounced activity against L1210 leukemia, which shows a natural partial resistance to doxorubicin itself. In the present study, lines of P388 leukemia and Ehrlich ascites tumor with acquired resistance to doxorubicin were found to be cross-resistant to 4'-O-methyldoxorubicin, indicating that the natural and the acquired resistance to doxorubicin involve different mechanisms. In vitro studies on the uptake of 4'-O-methyldoxorubicin in the Ehrlich ascites tumor cells indicated that the observed cross-resistance was partly due to a decreased drug uptake in the resistant cells because of an increased extrusion of the drug, in accordance with previous findings on the mechanism of acquired resistance to doxorubicin.

Absorption↗
PubMed1980

Antileukemic activity of 4-demethoxydaunorubicin in mice.

4-demethoxydaunorubicin was tested against experimental mouse leukemias, in comparison with doxirubicin and daunorubicin. 4-demethoxydaunorubicin, administered ip to mice bearing ascitic L1210 or P388 leukemia was 5 times more potent than daunorubicin and 10 times more potent than doxorubicin (potency established in relation to optimal antitumor doses). At the optimal doses, 4-demethoxydaunorubicin was as active as daunorubicin and less active than doxorubicin. 4-demethoxydaunorubicin, administered iv was 8 times more potent than daunorubicin and 4-5 times more potent than doxorubicin. At the optimal doses, 4-demethoxydaunorubicin was markedly more active than daunorubicin or doxorubicin in mice injected iv with 10(5) L1210 leukemia cells (early or late leukemia) or with 10(2) Gross leukemia cells. In mice given 2 X 10(6) Gross leukemia cells iv, 4-demethoxydaunorubicin was as active as doxorubicin when treatment was given iv on days 1, 5 and 9 for 4-demethoxydaunorubicin, and on days 1, 3 and 6 for daunorubicin and doxorubicin. 4-demethoxydaunorubicin administered orally was highly active against ascitic P388 leukemia and against L1210 and Gross leukemia inoculated iv.

Administration, Oral↗
PubMed1980

New anthracycline glycosides from Micromonospora. II. isolation, characterization and biological properties.

Four glycosides, designated A, B, C and D, are the main components of the anthracycline complex produced by cultures of Micromonospora sp. nov. They were extracted by solvent partition, separated by column chromatography and characterized by chemical and physical methods as 11-deoxy analogues of daunorubicin. Among these new anthracyclines, displaying antibacterial and cytotoxic activity in vitro, 11-deoxydaunorubicin and 11-deoxydoxorubicin are also active against P388 leukemia in mice.

Animals↗
PubMed1978

Enhancement of the antitumor activity of adriamycin by Tween 80.

This paper describes the effect of Tween 80 on the antitumor activity and on the distribution of adriamycin in mice. The dilution of adriamycin in a 10% water solution of Tween 80 produced a significant increase of the antitumor activity in mice against ascites tumors (L 1210 leukemia), disseminated leukemias (transplanted leukemias originally induced by Gross leukemai virus and Moloney leukemia virus), and solid tumors (Sarcoma 180, MS-2 sarcoma). In all these experiments the drug was administered i.v., according to different schedules. Higher antitumor activity at the optimal dose and an increase of activity at lower doses were observed in different experimental systems. Toxicity was also slightly enhanced. Tissue distribution was studied in normal mice and in tumor-bearing mice (Gross leukemia and MS-2 sarcoma). In animals give i.v. adriamycin diluted in 10% Tween 80 there was a higher drug concentration in spleen, lung and kidney than there was in mice given the drug in a water solution. In all the other organs examined (heart, liver, small intestine) and in the MS-2 tumor tissue, no significant increase was observed. In L1210 leukemia-bearing mice, i.p. treatment with adriamycin diluted in 10% Tween 80 resulted in a significantly higher toxicity than that which resulted from treatment with adriamycin in a wa ter solution; no increase of antitumor activity was observed.

Animals↗
PubMed1978

Effect of various substitutions in positions 1, 2, 3, and 4 of 4-demethoxydaunorubicin and 4-demethoxyadriamycin.

Previous studies on structure-activity relationships of anthracycline antitumor antibiotics have shown that removal of the methoxyl group at position 4 of the aglycone causes a marked increase in the potency of the compounds: 4-demethoxydaunorubicin and 4-demethoxyadriamycin had an antitumor effect similar to that of the parent compound at doses five to eight times lower, and they were active even when administered orally. This paper reports the effects of further substitutions at positions 1, 2, 3, and 4 of 4-demethoxy aglycone. The introduction of methyl groups at positions 2 and 3, or 1 and 4 resulted in decreased cytotoxicity and biological activity. The addition of a benzoyl ring at positions 2 and 3 decreased the activity further. 1,4-Dichloro-4-demethoxydaunorubicin and 2,3-dichloro-4-demethoxydaunorubicin were respectively as active and 2.5 times less active than was daunorubicin against HeLa cells in vitro while they were inactive against P388 and L1210 leukemias in vivo. 2,3-Dimethyl-4-demethoxyadriamycin showed an antitumor activity against mouse leukemias that was slightly higher than was that of adriamycin.

Animals↗
PubMed1978

Preparation and biological evaluation of 4-O-demethyldaunorubicin (carminomycin I) and of its 13-dihydro derivative.

A mutant strain of Streptomyces peucetius produced an anthracycline antibiotic whose structure has been established to be 4-O-demethyl-13-dihydrodaunorubicin (4), by application of spectroscopic methods and chemical degradation. A new synthesis of 4-O-demethyl-daunorubicin (carminomycin I, 2) starting from daunomycinone, together with the comparison of the antitumor activity of the anthracycline glycosides 2 and 4 are also reported.

Animals↗
PubMed1978

Antitumor activity of N-trifuloroacetyladriamycin-14-valerate.

The antitumor activity and toxicity of N-trifluoroacetyladriamycin-14-valerate (AD 32) dissolved in 10% Tween 80 in distilled water were compared to those of adriamycin dissolved in distilled water in 10% Tween 80 in distilled water, in mice bearing L1210 leukemia, P388 leukemia, Gross leukemia, and solid Sarcoma 180. Treatments were performed ip or iv according to different schedules. The antitumor-activity of AD 32 was not superior to that of adriamycin. The antitumor activity of adriamycin dissolved in aqueous solution of Tween 80 was higher than that of adriamycin dissolved in distilled water after after iv treatment.

Animals↗
PubMed1978

Synthesis and antitumor activity of 4-demethoxyadriamycin and 4-demethoxy-4' -epiadriamycin.

Two new analogs of adriamycin have been obtained by chemical synthesis, 4-demethoxyadriamycin and 4-demethoxy-4' -epiadriamycin. Both compounds were highly effective against experimental mouse tumors at doses about ten times lower than those effective for adriamycin. At the optimal dose, 4-demethoxyadriamycin displayed antitumor activity similar to that of adriamycin in solid Sarcoma 180 (S180), L1210, P388, and Gross leukemias, and mammary carcinoma, while it did not markedly inhibit the growth of Moloney sarcoma virus-induced sarcoma in mice treated before the virus infection. At the optimal dose, 4-demethoxy-4' -epiadriamycin was as active as adriamycin against L1210, P388,and Gross leukemias, and less active against solid S180. The results show that anthracycline derivatives characterized by the absence of the methoxyl group at the C-4 position are markedly more potent than the parent compound, and may exhibit a differential antitumor effect on a number of mouse tumors.

Animals↗
PubMed1977

Changes of activity of daunorubicin, adriamycin and stereoisomers following the introduction or removal of hydroxyl groups in the amino sugar moiety.

The results of a study of the effects of hydroxyl groups at positions, 2, 4 and 6 of the amino sugar on the activity of daunorubicin, adriamycin, and stereoisomers are presented. While the 4'-deoxy derivatives showed a slightly increased biological activity as compared with the parent compounds, the derivatives containing an additional hydroxyl group were less active. It is suggested that the changes in the polarity and in the DNA binding ability of these derivatives are the main factors accounting for the difference in the in vivo activity. The possible relations among the pKa values, the DNA binding properties, and the cellular uptake of the compounds are discussed with particular reference to their therapeutic effectiveness.

Animals↗
PubMed1976

Synthesis and antitumor activity of 4-demethoxydaunorubicin, 4-demethoxy-7,9-diepidaunorubicin, and their beta anomers.

Four new derivatives of daunorubicin, characterized by the absence of the methoxyl group at the C-4 position, have been obtained by chemical synthesis. 4-Demethoxydaunorubicin (NSC-256439) was effective against L1210 and Gross leukemias and ascites and solid Sarcoma 180 at doses four to eight times lower than those effective for daunorubicin. The beta anomer of 4-demethoxydaunorubicin was active at doses 13and eight times higher than those of its corresponding alpha anomer against L1210 and Gross leukemias respectively. 4-Demethoxy-7,9-diepidaunorubicin and its beta anomer were devoid of any biologic activity at the doses tested.

Animals↗