Mechanism of the Antimycoplasmal Activity of 2,2′-Bipyridyl Copper Complexes

Abstract

Some years ago we discovered the remarkable antimycoplasmal activity of the easily accesible l-amino-3-(2-pyridyl)isoquinolines^1,2. In these studies Mycoplasma gallisepticum, the causative agent of a respiratory disease in poultry, was used as the testorganism. It appeared that for antimycoplasmal activity in the isoquinoline series the presence of a 2,2′-bipyridyl system is a prerequisite together with ortho substitution towards the nitrogen atoms, a possibility of a cis coplanar conformation of the bipyridyl system and a certain degree of lipophilicity^3,4. Furthermore the presence of a trace of copper is necessary; without the addition of copper no activity could be established, while the copper itself at the concentrations used showed no inhibitory effect in the MlC-tests^5,6. From these results it was concluded that the combination of copper and the 2,2′-bipyridyl compound, i.e. a copper complex, causes the growth-inhibitory effect. A quantitative structure-activity relation study⁷ revealed an important contribution of the electronic character of the ortho substituents as well as their steric properties. An optimal lipophilicity log P_oct/water of 3.8 was found, although a small variation had only a slight effect on the antimycoplasmal activity. Nevertheless a certain extent of lipophilicity is necessary for antimycoplasmal activity.