Design, Synthesis, and Antimicrobial Activity of Quindoline Derivatives Inspired by the Cryptolepine Alkaloid

Abstract

Based on the structural characteristics of the cryptolepine alkaloid, a series of new quindoline derivatives bearing various substituents were prepared and evaluated for their fungicidal and antibacterial activities. Bioassay results showed that compound <b>D7</b> displayed superior <i>in vitro</i> fungicidal activities against <i>Sclerotinia sclerotiorum</i>, <i>Botrytis cinerea</i>, <i>Fusarium graminearum</i>, and <i>Rhizoctonia solani</i> with EC₅₀ values of 0.780, 3.62, 1.59, and 2.85 μg/mL, respectively. Compound <b>A7</b> showed apparent antibacterial activities toward <i>Xanthomonas oryzae</i> <i>pv. oryzae</i> with a minimum inhibitory concentration (MIC) value of 3.12 μg/mL. Significantly, <i>in vivo</i> antifungal activity suggested that the curative effect (98.3%) of compound <b>D7</b> was comparable to that of the positive control azoxystrobin (96.7%) at 100 μg/mL. Preliminary mechanistic studies showed that compound <b>D7</b> might cause mycelial abnormality of <i>S. sclerotiorum</i>, cell membrane breakage, accumulation of reactive oxygen species (ROS), and inhibition of sclerotia formation. Therefore, compound <b>D7</b> could be a novel broad-spectrum fungicidal candidate against plant fungal diseases.