Approaches to in-vitro lead generation for fungicide invention†

Abstract

There are increasing opportunities for the development of highthroughput in-vitro screens to aid the discovery of fungicides with novel modes of action. In the past, such screens were developed when biochemical targets were validated by fungicides with defined modes of action. However, genetic information is beginning to have a major impact both on the way in-vitro targets are selected and on the speed at which mode-of-action information is gained 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 investigations at Zeneca Agrochemicals, using inhibition of fungal respiration as an example. Saccharomyces cerevisiae is discussed as model for fungicide research, both in terms of its sensitivity to known fungicides and its well defined molecular genetics, which makes it amenable to such techniques as gene dosage for mode of action determination. © 1998 Society of Chemical Industry