Activity of Novel Tryptophan Analogs against Mammalian and Trypanosomal Monoamine Oxidases

Abstract

Monoamine oxidases were assayed in live Trypanosoma brucei brucei and in trypanosomal homogenate using the oxygen electrode method. Serotonin and tryptamine were used as standard monomine oxidase A and B substrates, respectively. The ability of live trypanosomes to metabolize tryptamine and serotonin was also monitored by the more sensitive high performance liquid chromatography method. No measurable enzyme activity could be detected in either live trypanosomes or trypanosomal cell homogenates. These results obtained suggest that T. b. brucei do not possess monoamine oxidase activity. Thus trypanocidal tryptophan analogs that were previously thought to act through inhibition of monoamine metabolizing enzymes may be acting by a diferent mechanism. The activity of these tryptophan analogs against mammalian MAO was tested to establish their potential toxicity in man. Two compounds, 5-(1-benzenesulphonylindol-2-ylidene)-5-methoxy-3-ethyl-thiazolidene-2-thione and 5-(1-benzenesulphonylindol-2-ylidene)-3- methylthiazolidine-2-thione had significant activity against mammalian monoamine oxidase. The enzyme kinetics for the latter was also derived.

Key words: Trypanosoma brucei brucei, monoamine oxidase, tryptophan metabolites.

East and Central African Journal of Pharmaceutical Sciences Vol.6(2) 2003: 43-49