Interplay of Target Activity and Biokinetic Behavior

The activity of a fungicide and its selectivity under real-life conditions in a complex system of the fungal pathogen, the plant, the environment, and time is determined by a multitude of quite different influencing factors [58]. In the optimization process of a lead structure it is useful to separate such influencing factors 

A decisive factor is the activity of the respective active substance for its molecular target in the fungus and potentially also in non-target organisms. With strobilurins, intrinsic activity is primarily determined by the binding affinity of the active substance to the Qo site of the bci complex of the respiratory chain (see Chapter 13.1 of this volume). 

Optimization of target activity is best done on the basis of a cell-free biochemical test that is as near to the isolated target protein as possible. If this is not possible, tests that are still near to the target should be used, for instance at the cellular level such tests can also often provide valuable complementary information to that obtained from a cell-free system. 

Equally important for in vivo activity under practical conditions is how much of the active substance actually succeeds in reaching its target. 

Of critical importance here are the particular characteristics of the molecule that govern its absorption, transportation, breakdown, and, where appropriate, excretion together, they help answer a critical question how much of the active substance is where, and when This seems a simple question, but to answer it empirically using the techniques of analytical chemistry generally requires high expenditures, and results available during optimization are thus limited and approximate. 

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