The effect of mannitol-myleran and two new dibromo-hexitols on the metabolic activities of nucleic acids and proteins—I.

Hidvégi, Egon J.; Lonai, Peter; Holland, John J.; Antoni, Ferenc András; Institóris, László; Horváth, István

doi:10.1016/0006-2952(67)90013-5

Cited by 15 publications

(3 citation statements)

References 17 publications

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“…A 10 mi. heparinized blood sample was collected at 0, ¥2, 1,2,4,8,12,24, and 48 hours with corresponding accumulated urine samples. All specimens were cooled on ice and immediately processed.…”

Section: Methodsmentioning

confidence: 99%

“…Renal excretion was the only apparent route of elimination of 1 4C-DBD, since neither expired and metabolites was rapid; 68 to 79 per cent of the administered radioactivity appeared in the urine within 48 hours. Chromatography of urine indicated the presence of unchanged DBD as well as 7 metabolic products.The metabolites tentatively identified are: monobromodulcitol; a diepoxy derivative,1,[2][3][4][5] an epoxide, anhydrodulcitol; dulcitol; and bromide ion. Two products remain unidentified.…”

mentioning

confidence: 99%

“…10 However, differences have been noted in the interaction of DBD with deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein when compared with that of typical alkylating agents. 4 The lack of antitumor activity of alkane homologues of DBD and the long half-life of the CH 2 -Br bond ( 5 to 6 hours) also suggest that part of the antitumor effect of DBD may be more dependent on other pharmacologic properties or metabolite formation than on alkylating capability. 6,7,9 Currently DBD has entered phase II clinical trials.…”

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confidence: 99%

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The absorption and metabolism of dibromodulcitol in patients with advanced cancer

Belej¹,

Troetel²,

Weiss³

et al. 1972

Clin Pharma and Therapeutics

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In patients with advanced cancer 1 4C-Dibromodulcitol (DBD) was rapidly absorbed from the gastrointestinal tract, entered the systemic circulation within 15 minutes after administration, and reached a maximum blood level within one hour. Plasma half-life of carbon-14 compounds was 8 hours. The drug was readily hydrolyzed in the plasma to monobromodulcitol and various epoxides so that within 2 hours after administration, less than 5 per cent of the unchanged drug remained. 1 4C-DBD compounds entered spinal, pleural, and ascitic fluids and reached a maximum concentration in 5 hours. Biopsy specimens indicated that DBD was present in both normal and malignant tissues. In autopsy specimens, radioactivity equivalent to 1 to 4 p.g of drug per gram of tissue was detectable for as long as 6 days after administration. Renal excretion was the only apparent route of elimination of 1 4C-DBD, since neither expired and metabolites was rapid; 68 to 79 per cent of the administered radioactivity appeared in the urine within 48 hours. Chromatography of urine indicated the presence of unchanged DBD as well as 7 metabolic products.The metabolites tentatively identified are: monobromodulcitol; a diepoxy derivative, 1,2-5,6-dianhydrodulcitol; an epoxide, anhydrodulcitol; dulcitol; and bromide ion. Two products remain unidentified.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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The absorption and metabolism of dibromodulcitol in patients with advanced cancer

Belej¹,

Troetel²,

Weiss³

et al. 1972

Clin Pharma and Therapeutics

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Clinical trials with the hexitol derivatives in the U.S.

Chiuten

Rozencweig

Hoff

et al. 1981

Cancer

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Three hexitol derivatives, dibromomannitol (DBM), dibromodulcitol (DBD), and dianhydrogalactitol (DAG), originally investigated in Hungary, have been evaluated as anticancer agents in the United States. Their principal mechanism of action is attributed to alkylation via actual or derived epoxide groups. Their preclinical spectrum includes activity against murine leukemias and against the murine ependymoblastoma, which is particularly noteworthy for DAG. Dibromomannitol trials were targeted to chronic myelogenous leukemia but no advantage over busulfan therapy was demonstrable. Dibromodulcitol and DAG were sequentially evaluated for their usefulness against a wide variety of tumors. The activity of DBD against breast cancer has stimulated several continuing trials in this disease. On the other hand, DAG was disappointing in breast cancer and in several other malignancies, but some activity has been noted against lung cancer. Both DBD and DAG are being investigated for possible usefulness in the management of patients with intracranial neoplasms. The present clinical experience does not allow firm judgment on the advantage of one analogue over another. Such comparative analysis does point out the desirable direction of future studies as well as the limitations of current preclinical systems for the selection of analogues.

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Apoptotic and Mitotic Activity in Squamous Cell Carcinoma Cells After Combined Modality Treatment With Γ‐irradiation and Dibromodulcitol

Kraxner

Tamás

Sáfrány

et al. 2001

Cell Biology International

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A-431 squamous cell carcinoma cells were treated in vitro with either 4 Gy radiation of 15 (or 45) microg/ml dibromodulcitol (DBD), as well as with combined 4 Gy irradiation and DBD, with the latter as either a pretreatment or post-treatment. DBD alone or in combination with radiation had a greater effect on cell proliferation than the effect of radiation alone. The difference is due to a higher level of apoptosis induced by DBD, especially in conjunction with radiation. Such a combination may therefore be useful in the treatment of squamous cell carcinoma, which in general responds poorly to radiation therapy.

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The effect of mannitol-myleran and two new dibromo-hexitols on the metabolic activities of nucleic acids and proteins—I.

Cited by 15 publications

References 17 publications

The absorption and metabolism of dibromodulcitol in patients with advanced cancer

The absorption and metabolism of dibromodulcitol in patients with advanced cancer

Clinical trials with the hexitol derivatives in the U.S.

Apoptotic and Mitotic Activity in Squamous Cell Carcinoma Cells After Combined Modality Treatment With Γ‐irradiation and Dibromodulcitol

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