Latentiated forms of the transport-inhibitory alpha-amino acid adamantanine

J Pharm Sci. 1980 Sep;69(9):1022-5. doi: 10.1002/jps.2600690911.

Abstract

N-(gamma-L-Glutamyl)adamantanine (Ic) and N-hydroxyadamantanine (Ib) were synthesized as latentiated forms of the transport-inhibitory alpha-amino acid adamantanine (Ia), and their biological properties were evaluated. Inhibition of the growth of P-388 tumor cells by Ib was comparable with that of the antitumor agent N-hydroxycycloleucine (IIb). In contrast, Ic was inactive in this system, presumably because it was not a substrate for gamma-glutamyltranspeptidase. Nevertheless, the concept proposed here of using the enzyme, gamma-glutamyltranspeptidase, to latentiate drugs in vivo by synthetic gamma-glutamylation of an amino or hydroxyl group on the drug molecule appears to be worthy of further exploration.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amantadine / analogs & derivatives*
  • Amantadine / chemical synthesis
  • Amantadine / pharmacology
  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Chemical Phenomena
  • Chemistry
  • Leukemia L1210 / drug therapy
  • Leukemia P388 / drug therapy
  • Male
  • Mice
  • Rats
  • gamma-Glutamyltransferase / antagonists & inhibitors

Substances

  • Antineoplastic Agents
  • N-hydroxyadamantanine
  • N-(gamma-glutamyl)adamantanine
  • Amantadine
  • gamma-Glutamyltransferase