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13 results on '"Loseto, F."'

1. Anti-leukaemic action of RuCl2(DMSO)4 isomers and prevention of brain involvement on P388 leukaemia and on subline

Author

A. Nassi, Loseto F, Enzo Alessio, Domenico Giordano, Mauro Coluccia, Gianni Sava, Angela Boccarelli, and Giovanni Mestroni

Subjects
Cisplatin, Cancer Research, DNA synthesis, DNA damage, Cell, Biology, In vitro, Peritoneal cavity, medicine.anatomical_structure, Oncology, Cell culture, Immunology, medicine, Cancer research, Cytotoxicity, medicine.drug
Abstract

Two ruthenium(II) complexes, characterised by the presence of dimethylsulphoxide ligands, were investigated in comparison to cisplatin on mouse P388 leukaemia and on a subline made resistant to cisplatin (P388/DDP). Both cis- and trans-RuCl2(DMSO)4 significantly prolonged the survival time of leukaemic mice, independently of the tumour line used. Unlike cisplatin, the prolongation of life-span of tumour-bearing hosts caused by ruthenium complexes was not supported by a parallel inhibition of the number of tumour cells in the treated hosts, as evidenced by tumour cell count in the peritoneal cavity and by vivo-vivo bioassays of blood samples and of whole brains. Thus, cis- and trans-RuCl2(DMSO)4 appear capable of preventing leukaemic spread into the central nervous system also when the number of tumour cells in the peritoneal cavity and in the blood stream is as high as in untreated controls. When the drug-induced DNA damage was investigated by modifying double stranded DNA and identifying the lesions able to inhibit DNA synthesis in vitro, trans-RuCl2(DMSO)4 and, to a lesser extent, cis-RuCl2(DMSO)4 formed blocking lesions at the same sites of cisplatin; nevertheless, the mechanism of antitumour activity of ruthenium complexes appears to be different from that of cisplatin for the absence of any relationship between cytotoxicity and prevention of leukaemic dissemination into the central nervous system. These data indicate that the activity of cis- and trans-RuCl2(DMSO)4 on the P388 leukaemia is characterised by the lack of cross-resistance with cisplatin and by the alteration of the metastasising behaviour of leukaemic cells which lose their natural capacity to invade the central nervous system.

Published
1993
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2. A trans-platinum complex showing higher antitumor activity than the cis congeners

Author

Domenico Giordano, Paola A. Caputo, Giovanni Natile, Loseto F, Angela Boccarelli, Francesco P. Intini, A. Nassi, Maria A. Mariggiò, and Mauro Coluccia

Subjects
Cisplatin, Antitumor activity, Molecular Structure, Leukemia P388, Stereochemistry, Chemistry, Antineoplastic Agents, Stereoisomerism, Biological activity, Tumor cells, DNA, Mice, Drug Discovery, medicine, Animals, Molecular Medicine, Platinum complex, Imines, P388 leukemia, Cytotoxicity, Ethers, medicine.drug
Published
1993
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4. Interaction of RuCl2(DMSO)4 isomers with DNA

Author

Loseto, F., Alessio, Enzo, Mestroni, G., Lacidogna, G., Nassi, A., Giordano, D., Coluccia, M., F., Loseto, Alessio, Enzo, G., Mestroni, G., Lacidogna, A., Nassi, D., Giordano, and M., Coluccia

Subjects
anticancer metal compounds, ruthenium, DNA, anticancer metal compound
Published
1991

11. Interaction of RuCl2 (dimethylsulphoxide)4 isomers with DNA.

Author

Loseto F, Alessio E, Mestroni G, Lacidogna G, Nassi A, Giordano D, and Coluccia M

Subjects
Base Sequence, DNA Restriction Enzymes antagonists & inhibitors, Molecular Sequence Data, Restriction Mapping, DNA Restriction Enzymes metabolism, DNA, Bacterial chemistry, Dimethyl Sulfoxide analysis, Plasmids
Abstract

A wide series of restriction enzymes with a range of specificities was used to investigate the interaction with DNA of Ru(II)-DMSO complexes with anticancer activity. While cis-RuCl2 (DMSO)4 was almost completely inactive, treatment of pBR 322 DNA with trans-RuCl2 (DMSO)4 protected G rich sequences from cutting of specific restriction endonucleases, indicating a preferential interaction with adjacent guanines.

Published
1991

12. Synthesis, mutagenicity, binding to pBR 322 DNA and antitumour activity of platinum(II) complexes with ethambutol.

Author

Coluccia M, Fanizzi FP, Giannini G, Giordano D, Intini FP, Lacidogna G, Loseto F, Mariggio MA, Nassi A, and Natile G

Subjects
Animals, Binding Sites, Ethambutol chemical synthesis, Ethambutol therapeutic use, Male, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Inbred Strains, Molecular Structure, Mutagenicity Tests, Organoplatinum Compounds chemical synthesis, Organoplatinum Compounds therapeutic use, Restriction Mapping, Salmonella typhimurium drug effects, Antineoplastic Agents therapeutic use, Cisplatin pharmacology, Ethambutol analogs & derivatives, Ethambutol pharmacology, Leukemia P388 drug therapy, Lung Neoplasms drug therapy, Mutagens pharmacology, Organoplatinum Compounds pharmacology, Plasmids
Abstract

Platinum complexes with N,N'-bis(1-hydroxybut-2-yl)ethylenediamine, [PtCl2(ethambutol)] were prepared and the biological activity of three isomers [with (-), (+) and (+/-) ethambutol, respectively] investigated. All species interact with the Bam HI and Ava I recognition sequences showing a binding preference for GC rich sequences of DNA. The complex which showed the greatest interaction with adjacent guanines, [PtCl2[+/-)ethambutol)] was also found to be the most mutagenic of the three. On the other hand, only [PtCl2[+)ethambutol)] had a considerable antitumour activity against both P388 leukaemia and Lewis lung carcinoma, and this was not correlated either with restriction enzyme blocking activity or with mutagenicity.

Published
1991

13. Different binding to DNA of enantiomeric platinum complexes assessed by inhibition of restriction enzyme activity.

Author

Coluccia M, Giordano D, Loseto F, Intini FP, Maresca L, and Natile G

Subjects
Cisplatin metabolism, Organoplatinum Compounds metabolism, Platinum pharmacology, Stereoisomerism, Antineoplastic Agents metabolism, DNA metabolism, DNA Restriction Enzymes antagonists & inhibitors, Platinum metabolism
Abstract

The ability of enantiomeric platinum complexes to block the action of selected restriction enzymes has been investigated. The complexes [PtCl2(DAC)], [PtCl2(DAB)] and [PtCl2(DAP)] (DAC = 1,2-diamminocyclohexane; DAB = 2,3-diamminobutane; DAP = 1,2-diamminopropane) exhibit a guanine-cytosine preference in accord with previous results on cis-[PtCl2(NH3)2] (cis-DDP). The extent of inhibition, however, is significantly different for the different isomers; the R,R form is more active than the others at short incubation time, as the time becomes longer, the differences among isomers level off. It also appears that cis-DDP is more active than [PtCl2(DAC)] in blocking the Cfo I enzyme, though it shows a preference for the G-X-G sequences.

Published
1989

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