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.