.alpha.-Ethynyl and .alpha.-vinyl analogs of ornithine as enzyme-activated inhibitors of mammalian ornithine decarboxylase

Abstract
.alpha.-Ethynyl- and .alpha.-vinylornithine were designed and synthesized as potential enzyme-activated inhibitors of mammalian ornithine decarboxylase. The 2 new inhibitors produce both immediate and time-dependent inhibition of rat liver ornithine decarboxylase in vitro. The inhibitions exhibit saturation kinetics. The apparent dissociation constants (KI) are 10 and 810 .mu.M and the times of half-inactivation at infinite concentration of inhibitor (t1/2) are 8.5 and 27 min, respectively, for .alpha.-ethynyl- and .alpha.-vinylornithine. In rats, .alpha.-ethynylornithine causes a rapid dose-dependent decrease of ornithine decarboxylase EC 4.1.1.17 activity in prostate and in thymus and testis.