Approaches to in-vitro lead generation for fungicide invention

There are increasing opportunities for the development of high-throughput i n-vitro screens to aid the discovery of fungicides with novel modes of acti on. In the past, such screens were developed when biochemical targets were validated by fungicides with defined modes of action. However, genetic info rmation is beginning to have a major impact both on the way in-vitro target s are selected and on the speed at which mode-of-action information is gain ed on current fungicides having an, as yet, undefined mode of action. This paper discusses issues concerning target selection and high-throughput screening, using examples taken from the current literature and from inves tigations at Zeneca Agrochemicals, using inhibition of fungal respiration a s an example. Saccharomyces cerevisiae is discussed as model for fungicide research bath in terms of its sensitivity to known fungicides and its well defined molecu lar genetics, which makes it amenable to such techniques as gene dosage for mode of action determination (C) 1998 Society of Chemical Industry.