DISEÑO RACIONAL DE FORMULACIONES BIOCOMPATIBLES DE NUEVOS ANTIFUNGICOS PARA SU APLICACIÓN EN AGRICULTURA SUSTENTABLE

HERRERA CANO, NATIVIDAD

Simposio; XXXVII Reunión Científica Anual Sociedad de Biología de Cuyo; 2019

Botrytis cinerea (B. cinerea) is a fungus that causes gray mold. This is a disease which induces the decay and deterioration of grape berries by altering its chemical composition. The organoleptic properties, such as the taste and color of wine, are affected. Its control is difficult because the fungus is genetically variable and has developed strains resistant to many of the chemicals in the last years. In addition, the indiscriminate use of fungicides has increased the development of microbial resistance in medicine and agriculture. Hence, it is essential to discover new low toxic substances. Based on this, a comprehensive study has been carried out in our working group. It includes: the synthesis of new antifungals, the design of biocompatible formulations, the evaluation of their bioactivity against B. cinerea, and the study of the mechanism of action of new entities, through molecular modeling.A family of compounds was accomplished by the arylation of the commercial fungicides triadimefon (1) and cyproconazole (2), via two different methodologies (SRN1-Stille reaction or Suzuki reaction). The bioactivity was proved against B. cinerea, isolated from infected grapes in the province of San Juan, Argentina. The results showed that the monofluorinated compound (3) was the most active, and turn levels of cytotoxicity were comparable to commercial fungicides. Furthermore, molecular modeling studies demonstrated that this derivative displayed interactions with the active site of the enzyme very similar to those observed with 2 and voriconazole.These results encouraged us to continue the study in search of the ideal, more effective and less toxic agrochemical than commercial ones. For this purpose, two strategies were studied. One of them was the combination of synthetic antifungal (3) with citral, an essential oil of recognized activity against B. cinerea. The other one was the design of biocompatible formulations of derivative 3 using chitosan as a biodegradable polymer. Cytotoxicity studies are currently underway, with the aim of confirming whether these formulations are less toxic than their precursors.This work constitutes a contribution to the redesign of more effective and safer agrochemicals for their potential application in sustainable agriculture.