Synthesis and mechanistic studies of phosphoraziridines as radiation sensitizers
Thesis/Dissertation
·
OSTI ID:6766435
Ethyl bis(2,2-dimethyl-1-aziridinyl)phosphinyl carbamate (AB-132) and ethyl bis(2,2-dimethyl-1-aziridinyl)phosphinate (AB-163) are potent antitumor agents which have also been demonstrated to be radiation sensitizers in experimental and clinical studies. Monophenyl aziridines and various isomers of diphenylaziridines were utilized. Optically active 2-phenyl aziridine was also employed in order to prepare diastereomerically homogeneous compounds. Para-substituted phenylaziridines were prepared as well and converted to the corresponding phosphoraziridines in order to probe electronic effects of such substituents on biological activity and chemical reactivity. The hydrolysis of 2,2-dimethylaziridine-type compounds including AB-132 and AB-163 was studied by NMR in order to gain further insight into the hydrolytic intermediates which may be responsible for the known cholinesterase inhibition and the suspected phosphorylation of radiation-damaged DNA. Comparative reactivities of the compounds prepared in this study with p-nitrobenzylpyridine were investigated so as to provide some indication of potential alkylating activity, in the hope of obtaining a correlation with biological activity. Electron spin resonance was utilized to study the effects of radiation on phosphoraziridine crystals.
- OSTI ID:
- 6766435
- Country of Publication:
- United States
- Language:
- English
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Journal Article
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Sun Mar 31 23:00:00 EST 1991
· Journal of Medicinal Chemistry; (USA)
·
OSTI ID:5639476
Chemical mechanism of the radiation potentiating effects of 2,2-dimethylaziridine-type antitumor agents
Conference
·
Sat Sep 01 00:00:00 EDT 1979
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·
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Radiation potentiating effect of ethyl bis(2,2-dimethyl-l-aziridinyl) phosphinate (AB-163)
Conference
·
Sat Sep 01 00:00:00 EDT 1979
· Int. J. Radiat. Oncol., Biol. Phys.; (United States)
·
OSTI ID:5275165
Related Subjects
550600* -- Medicine
560100 -- Biomedical Sciences
Applied Studies-- Radiation Effects
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANTINEOPLASTIC DRUGS
BIOLOGICAL EFFECTS
CARBOXYLESTERASES
CHEMICAL REACTIONS
CHOLINESTERASE
DNA
DRUGS
ENZYME INHIBITORS
ENZYMES
ESTERASES
HYDROLASES
MAGNETIC RESONANCE
NUCLEAR MAGNETIC RESONANCE
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PHOSPHORYLATION
RADICALS
RADIOSENSITIZERS
REACTION INTERMEDIATES
RESONANCE
SYNTHESIS
560100 -- Biomedical Sciences
Applied Studies-- Radiation Effects
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANTINEOPLASTIC DRUGS
BIOLOGICAL EFFECTS
CARBOXYLESTERASES
CHEMICAL REACTIONS
CHOLINESTERASE
DNA
DRUGS
ENZYME INHIBITORS
ENZYMES
ESTERASES
HYDROLASES
MAGNETIC RESONANCE
NUCLEAR MAGNETIC RESONANCE
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PHOSPHORYLATION
RADICALS
RADIOSENSITIZERS
REACTION INTERMEDIATES
RESONANCE
SYNTHESIS