FURTHER STUDIES OF THE ANTIMYCOBACTERIAL AGENTS GLYCYL HYDROXAMIC ACID AND β-ALANYL HYDROXAMIC ACID

Abstract

An investigation was made of certain pharmacological and chemical characteristics of the antimycobacterial agents glycyl hydroxamic acid (GHA) and β-alanyl hydroxamic acid (BAHA). Inhibition by GHA of the growth of Mycobacterium smegmatis was antagonized by D-, L-, and DL-alanine, pyridoxal phosphate (PyP), and ascorbic acid. Inhibition by BAHA was reversed by D-alanine. Oxidation of L-alanine by the organism was inhibited by GHA, and this inhibition was partially antagonized by PyP and by L-alanine. BAHA had virtually no effect on oxidation of L-alanine. GHA inhibited the dihydroxyphenylalanine (DOPA) decarboxylase from guinea pig liver, and this inhibition was antagonized by PyP. BAHA was without effect on DOPA decarboxylase. Ultraviolet absorption spectroscopy suggested an alteration of PyP by GHA and BAHA. The test for hydroxylamine was found unsuitable as a means for determining stability of each compound due to falsely high values. Synthesis of each compound is described in an appendix.