Abstract

The inactivation of proline dehydrogenase by several l-Pro analogues was investigated with the aim to block the essential metabolic pathway of tsetse flies allowing the degradation of l-Pro to l-Glu. In vitro studies on rat liver mitochondria showed that only 4-methylene- l-proline was able to inactivate proline dehydrogenase. The inactivation kinetics agreed with a mechanism-based inhibition. The other tested analogues E- and Z-4- fluoromethylene- l-proline , and cis and trans-5- ethyl- d,l-proline were neither substrate nor inactivator of the enzyme. In vivo 4-methylene- l-proline showed no toxicity against Drosophila flies, but was lethal for Glossina pallidipes flies. This result allows the consideration of 4-methylene- l-proline as an attractive compound molecule in the struggle against tsetse flies.

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