Design, Synthesis, and Antifungal Evaluation of Novel Quinoline Derivatives Inspired from Natural Quinine Alkaloids

Abstract

Inspired by quinine and its analogues, we designed, synthesized, and evaluated two series of quinoline small molecular compounds (<b>a</b> and <b>2a</b>) and six series of quinoline derivatives (<b>3a</b>-<b>f</b>) for their antifungal activities. The results showed that compounds <b>3e</b> and <b>3f</b> series exhibited significant fungicidal activities. Significantly, compounds <b>3f-4</b> (EC₅₀ = 0.41 μg/mL) and <b>3f-28</b> (EC₅₀ = 0.55 μg/mL) displayed the superior in vitro fungicidal activity and the potent in vivo curative effect against <i>Sclerotinia sclerotiorum</i>. Preliminary mechanism studies showed that compounds <b>3f-4</b> and <b>3f-28</b> could cause changes in the cell membrane permeability, accumulation of reactive oxygen species, loss of mitochondrial membrane potential, and effective inhibition of germination and formation of <i>S. sclerotiorum</i> sclerotia. These results indicate that compounds <b>3f-4</b> and <b>3f-28</b> are novel potential fungicidal candidates against <i>S. sclerotiorum</i> derived from natural products.