Bioactivity-Guided Subtraction of MIQOX for Easily Available Isoquinoline Hydrazides as Novel Antifungal Candidates

Thediscovery of novel and easily available leads provides a convincingsolution to agrochemical innovation. A bioassay-guided scaffold subtractionof the previous Chem-Bio Model isoquinoline-3-oxazoline MIQOX was conducted for identifying the easily available isoquinoline-3-hydrazideas a novel antifungal scaffold. The special and practical potentialof this model was demonstrated by a phenotypic antifungal bioassay,molecular docking, and cross-resistance evaluation. A panel of antifungalleads (LW2, LW3, and LW11)was acquired, showing much better antifungal performance than thepositive controls. Specifically, compound LW3 exhibiteda broad antifungal spectrum holding EC50 values as lowas 0.54, 0.09, 1.52, and 2.65 mg/L against B. cinerea, R. solani, S. sclerotiorum , and F. graminearum, respectively.It demonstrated a curative efficacy better than that of boscalid incontrolling the plant disease caused by B. cinerea. The candidate LW3 did not show cross-resistance tothe extensively used succinate dehydrogenase inhibitor (SDHI) fungicidesand can efficiently inhibit resistant B. cinerea strains. The molecular docking of compound LW3 is quitedifferent from that of the positive controls boscalid and fluopyram.This progress highlights the practicality of isoquinoline hydrazideas a novel model in fungicide innovation.

Automated summary

A novel antifungal scaffold, isoquinoline-3-hydrazides, was identified through a bioassay-guided scaffold subtraction. The compound LW3 showed a broad-spectrum antifungal activity and no cross-resistance to commonly used fungicides. This finding highlights the practical potential of isoquinoline hydrazides as a novel model in fungicide innovation.