Drought is the most destructive force in agriculture, causing annual losses of nearly 40 billion dollars worldwide. The FAO and UN have therefore emphasized the urgent need for innovative strategies to improve crop performance under water-limiting conditions. One effective approach is the activation of abscisic acid (ABA) signaling, which induces stomatal closure and broad physiological adjustments that enhance plant stress tolerance. In this work, we applied a drug discovery approach to identify and optimize small-molecule ABA- receptor agonists for crop protection. A chemical library of 60,000 molecules was screened in vitro, leading to the discovery of novel scaffolds not previously described in scientific or patent literature. Through iterative cycles of structure-guided design, synthesis, and validation, we generated and characterized over 100 new compounds, ultimately defining a chemical series of 10 molecules with enhanced properties. Among them, Superabactin emerged as a potent sulfonamide-based agonist with 10-fold higher activity than ABA. Superabactin activates ABA signaling in tomato, wheat, and maize, reduces transpiration when applied as a foliar spray, and increases water-use efficiency. Remarkably, a single treatment induces stomatal closure for up to two weeks in maize, conserving soil moisture and improving drought tolerance. These results highlight the potential of medicinal chemistry and chemical biology as powerful tools to develop next-generation biostimulants for sustainable agriculture.
Poster
