Discovery and development of new compounds aiming to control Moniliophthora perniciosa, the causal agent of Witches' Broom Disease of cocoa, based on the inhibition of the cellular respiration

Abstract

Brazil is the third largest agricultural producer in the world, but is the greatest consumer of pesticides. The reason for this discrepancy is the fact that pesticides are primarily designed to act on temperate regions, where developed countries are situated. Therefore, it is commonly found that those pesticides are not effective against tropical phytopathogens, and increasing usage doses are employed in order to achieve desirable effects. Such an example is the witches' broom disease of cocoa, caused by the basidiomycete fungus Mniliophthora perniciosa. This disease devastated Brazilian cocoa farms in the early 1990's, with important social and economic consequences. Since the year of 2000, our research group has been researching in order to understand M. perniciosa at the molecular level and to unveil new methods to control this pathogen. A first step has been made, and crop management recommendations have been issued based on our discoveries, which have been thoroughly divulged and have significantly contributed to the recovery of cocoa farms. However, a fundamental point will be the development of a new molecule that is able to control M. perniciosa in the field. Throughout years of research, we have unveiled that this pathogen depends on the enzyme Alternative Oxidase (AOX) to complete the disease cycle and to survive. The inhibition of that enzyme, in conjunction with cellular respiration inhibitors, kills the fungus. Even more appealing, is the fact that the same combination of drugs is effective against other fungi of relevance to the Brazilian agribusiness. Therefore, the aim of this project is to create new AOX inhibitors with potential to be employed as a commercial fungicides, and this will be achieved through the integration of specialists in the areas of molecular plant pathology, structural biology and medicinal chemistry. We understand that this is a unique opportunity for our country to become a key player in the development of pesticides aimed at tropical cultures, especially considering that Brazil is expected to be the major world food producer until 2025. (AU)