Latentiated forms of the transport-inhibitory alpha-amino acid adamantanine.
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.
D000547:Amantadine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D008297:Male; D051379:Mice; D051381:Rats; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; C026743:N-hydroxyadamantanine; C026744:N-(gamma-glutamyl)adamantanine; D000547:Amantadine; D005723:gamma-Glutamyltransferase