In the search for new anticancer drugs. 13. Phosphonic and phosphinic analogues of ornithine.
Phosphonic (4a,b) and phosphinic (5a-d) analogues of ornithine were synthesized and evaluated for their inhibitory activity against ornithine decarboxylase and against the lymphocytic leukemia P388. The title compounds possess a low degree of inhibition against rat liver ornithine decarboxylase as compared to alpha-(difluoromethyl)ornithine. Thus, compounds 4a and 5a inhibit by 40% the ornithine decarboxylase activity at a 5 mM concentration. The other derivatives are less potent. Compounds 4a, 4b, 5b, and 5d are inactive against P388 tumor in CD2F1 mice at doses of 50 and 150 mg/kg.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D007941:Leukemia P388 / Q000188:drug therapy; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D063065:Organophosphonates; D009952:Ornithine / Q000031:analogs & derivatives*; D065108:Ornithine Decarboxylase Inhibitors; D010721:Phosphinic Acids; D051381:Rats; D011919:Rats, Inbred Strains
D000970:Antineoplastic Agents; D063065:Organophosphonates; D065108:Ornithine Decarboxylase Inhibitors; D010721:Phosphinic Acids; D009952:Ornithine