[The toxicity and biological effects of organophosphorus epoxides].
In the series of glycidylic ethers of alkylophosphoric and methylphosphoric acids three types of compounds have been identified: those possessing anticholinesterase, narcotic, and antineoplastic activity. Monoglycidylic ethers of diethyl- and diisopropylphosphoric acids and diglycidylic ether of ethylphosphoric acid caused intoxication of animals with the cholinergic excitation syndrome, and in vitro in a concentration of 1 mmol/liter strongly inhibited cholinesterase, stimulated the motor activity of an intestinal segment, but did not demonstrate cytotoxic activity in relation to NK/Ly strain tumor cells. Monoglycidylic ethers of di-n-propyl-, di-iso-butyl, and di-n-butyl-phosphoric acids as well as diglycidylic ethers of n-butyl- and iso-amylphosphoric acids caused a "hypnotic state" in the animals, suppressed the motor activity of an isolated intestinal segment, considerably increased the number of diffusely stained by Aĭzenman's [correction of Aisenmanns'] method cells of ascitic NK/Ly tumor in vitro, but poorly inhibited the growth of this tumor in chemotherapeutic experiments. Diglycidylic ethers of methyl-, n-propyl-, iso-butylphosphoric, and methylphosphonic acids caused poisoning of the type of intoxication by alkylating agents, weakly influenced cholinesterase activity, did not change the character of contractions of the intestinal segment. In vitro they caused a strong cytotoxic effect, but delayed the growth of the NK/Ly tumor treated animals by 84-100%. The possibility of the phosphororganic epoxides under study taking part in the reactions of alkylation and phosphorylation is suggested.
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D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity*; D001921:Brain / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity*; D002802:Cholinesterases / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004852:Epoxy Compounds / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity*; D007421:Intestine, Small / Q000187:drug effects; D007928:Lethal Dose 50; D008223:Lymphoma / Q000188:drug therapy; D051379:Mice; D009368:Neoplasm Transplantation; D009943:Organophosphorus Compounds / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity*; D011817:Rabbits; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002800:Cholinesterase Inhibitors; D004852:Epoxy Compounds; D009943:Organophosphorus Compounds; D002802:Cholinesterases