Carla Jean Rasmussen Klittich

Can agricultural fungicides accelerate the discovery of human antifungal drugs

Twelve drugs from four chemical classes are currently available for treatment of systemic fungal infections in humans. By contrast, more than 100 structurally distinct compounds from over 30 chemical classes have been developed as agricultural fungicides, and these fungicides target many modes of action not represented among human antifungal drugs. In this article we introduce the diverse aspects of agricultural fungicides and compare them with human antifungal drugs. We propose that the information gained from the development of agricultural fungicides can be applied to the discovery of new mechanisms of action and new antifungal agents for the management of human fungal infections.

Assessment of fungicide systemicity in wheat using LC-MS/MS.

BACKGROUND Systemicity is an important attribute of fungicides that is difficult to measure in early-stage screening without labeling the compound with a radioisotope. A method of measuring translocation that does not require potent fungicidal activity or a radiolabel would guide identification of compounds with desirable attributes. RESULTS The authors developed an analytical technique that mimics field application, using LC-MS/MS to screen compounds for translocation in wheat leaves. The method sorted commercial and experimental fungicides appropriately into systemic and non-systemic categories. A model using LC-MS/MS data was equivalent to a lipophilicity model and superior to a water solubility model at predicting compound systemicity. CONCLUSION Early-stage compounds can be screened for systemicity on whole plants using LC-MS/MS.

Effects of physical properties on the translaminar activity of fungicides.

Translaminar redistribution is a key component of activity for many fungicides. The influence of physical properties (including water solubility, lipophilicity, melting point, and molar volume) on translaminar activity, however, is not well understood. Cucumber powdery mildew was used as a biological indicator to examine the influence of physical properties on translaminar activity of 61 fungicides in simple, uniform formulations, including three modes-of-action and a range of physical properties. Results were modeled using multiple regression and ordinal logistic fit. We confirmed that translaminar activity is a frequent attribute of fungicides and that lipophilicity and water solubility are important predictors of translaminar activity. The hypothesis that melting point drives translaminar movement and translaminar activity was not supported. Translaminar movement (driven only by physical properties) could be differentiated with the models from fungitoxicity-influenced translaminar control. Translaminar activity is a complex attribute and differences in inherent activity as well as physical properties and formulations must be considered when comparing compounds for relative translaminar activity.

Physicochemical property guidelines for modern agrochemicals: Physicochemical properties for agrochemicals

The relentless need for the discovery and development of new agrochemicals continues as a result of driving forces such as loss of existing products through the development of resistance, the necessity for products with more favorable environmental and toxicological profiles, shifting pest spectra, and the changing agricultural needs and practices of the farming community. These new challenges underscore the demand for novel, high-quality starting points to accelerate the discovery of new agrochemicals that address market challenges. This article discusses the efforts to identify the optimum ranges of physicochemical properties of agrochemicals through analysis of modern commercial products. Specifically, we reviewed literature studies examining physicochemical property effects and analyzed the properties typical of successful fungicides, herbicides, and insecticides (chewing and sap-feeding pests). From the analysis, a new set of physicochemical property guidelines for each discipline, as well as building block class, are proposed. These new guidelines should significantly aid in the discovery of next-generation agrochemicals.