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

• Published in: Journal of agricultural and food chemistry 2022-03, Vol.70 (9), p.2851-2863
• Main Authors: Chu, Qing-Ru, He, Ying-Hui, Tang, Chen, Zhang, Zhi-Jun, Luo, Xiong-Fei, Zhang, Bao-Qi, Zhou, Yong, Wu, Tian-Lin, Du, Sha-Sha, Yang, Cheng-Jie, Liu, Ying-Qian
• Format: Article
• Language: English
• Subjects: Agricultural and Environmental Chemistry; Alkaloids; Antifungal Agents - chemistry; Fungicides, Industrial - chemistry; Indole Alkaloids - chemistry; Indole Alkaloids - pharmacology; Indoles; Molecular Structure; Quinolines; Structure-Activity Relationship
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.1c07536

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