4 research outputs found
Bioactivity-Guided Subtraction of MIQOX for Easily Available Isoquinoline Hydrazides as Novel Antifungal Candidates
The
discovery of novel and easily available leads provides a convincing
solution to agrochemical innovation. A bioassay-guided scaffold subtraction
of the previous “Chem-Bio Model” isoquinoline-3-oxazoline MIQOX was conducted for identifying the easily available isoquinoline-3-hydrazide
as a novel antifungal scaffold. The special and practical potential
of this model was demonstrated by a phenotypic antifungal bioassay,
molecular docking, and cross-resistance evaluation. A panel of antifungal
leads (LW2, LW3, and LW11)
was acquired, showing much better antifungal performance than the
positive controls. Specifically, compound LW3 exhibited
a broad antifungal spectrum holding EC50 values as low
as 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 in
controlling the plant disease caused by B. cinerea. The candidate LW3 did not show cross-resistance to
the extensively used succinate dehydrogenase inhibitor (SDHI) fungicides
and can efficiently inhibit resistant B. cinerea strains. The molecular docking of compound LW3 is quite
different from that of the positive controls boscalid and fluopyram.
This progress highlights the practicality of isoquinoline hydrazide
as a novel model in fungicide innovation