Synthesis and anticancer activity of novel cyclic N-hydroxyureas.
To overcome the disadvantages of hydroxyurea in anticancer therapy such as fast biotransformation and low potency, five cyclic N-hydroxyureas were synthesized. A new reaction was developed to prepare the desired products from the appropriate alkyl omega-haloalkylcarbamates with hydroxylamine. This reaction probably involves a two-step mechanism: nucleophilic substitution and intramolecular cyclization. The anticancer screening tests of these compounds were done both in vitro using tissue culture and in vivo. One compound, 1-hydroxy-1,3-diazacylohexan-2-one, had anticancer activity comparable to hydroxyurea both in vivo and in vitro.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003500:Cyclization; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000188:drug therapy
D000970:Antineoplastic Agents; D006918:Hydroxyurea