Biologic activity of two derivatives and six possible metabolites of cyclophosphamide (NSC 26271)
article
The biologic activity in terms of survival of normal hematopoietic stem, osteosarcoma, and L1210 leukemia cells was determined for the following compounds: cyclophosphamide, its derivatives isophosphamide and trophosphamide, its possible metabolites nor nitrogen mustard, hydroxylamine mustard, 4 ketocyclo phosphamide, and acrolein, and two substitutes for its primary active metabolite 4 hydroxycyclophosphamide anhydro dimer (4 hydroxy CP anhydro dimer) and 4 hydroperoxycyclophosphamide (4 hydroperoxy CP). On a molar basis none of the compounds shows a better therapeutic ratio between osteosarcoma and bone marrow stem cells than the parent compound. The therapeutic ratio between L1210 leukemia and normal cells is slightly better for 4 hydroperoxy CP only. It may be concluded that the conversion of 4 hydroxy CP anhydro dimer and 4 hydroperoxy CP to the primary active metabolite 4 hydroxycyclophosphamide differs quantitatively. Moreover, it appears that by the use of these precursors a better therapeutic ratio might be obtained for some malignancies but not for others.
Chemicals/CAS: 4 oxocyclophosphamide, 27046-19-1; acrolein, 107-02-8; alcohol, 64-17-5; carboxymethylcellulose, 8050-38-2, 9000-11-7, 9004-32-4, 9050-04-8; cyclophosphamide, 50-18-0; dichlorodiethylamine, 334-22-5, 821-48-7; dimethyl sulfoxide, 67-68-5; hydroxylamine, 7803-49-8; ifosfamide, 3778-73-2; sodium chloride, 7647-14-5; trofosfamide, 22089-22-1; Acrolein, 107-02-8; Antineoplastic Agents; Cyclophosphamide, 50-18-0; Ifosfamide, 3778-73-2; Nitrogen Mustard Compounds; Oxazines
Chemicals/CAS: 4 oxocyclophosphamide, 27046-19-1; acrolein, 107-02-8; alcohol, 64-17-5; carboxymethylcellulose, 8050-38-2, 9000-11-7, 9004-32-4, 9050-04-8; cyclophosphamide, 50-18-0; dichlorodiethylamine, 334-22-5, 821-48-7; dimethyl sulfoxide, 67-68-5; hydroxylamine, 7803-49-8; ifosfamide, 3778-73-2; sodium chloride, 7647-14-5; trofosfamide, 22089-22-1; Acrolein, 107-02-8; Antineoplastic Agents; Cyclophosphamide, 50-18-0; Ifosfamide, 3778-73-2; Nitrogen Mustard Compounds; Oxazines
Topics
4 oxocyclophosphamideacroleinalcoholcarboxymethylcellulosechlormethine derivativecyclophosphamidecyclophosphamide derivativedichlorodiethylaminedimethyl sulfoxidehydroxylamineifosfamidesodium chloridetrofosfamidebone marrow transplantationcell culturedrug analysisdrug toxicityimmunosuppressive treatmentin vitro studyleukemia l 1210mouseosteosarcomaspleen celltheoretical studyAcroleinAnimalAntineoplastic AgentsBiotransformationCells, CulturedCyclophosphamideDose-Response Relationship, DrugFemaleHematopoietic Stem CellsHydroxylationIfosfamideLeukemia L1210MaleMiceMice, Inbred C57BLMice, Inbred CBAMice, Inbred DBANeoplasms, ExperimentalNitrogen Mustard CompoundsOsteosarcomaOxazines
TNO Identifier
228060
Source
Cancer Rreatment Report, 60(4), pp. 373-379.
Pages
373-379
Files
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