Design, Synthesis, and Antifungal Evaluation of Neocryptolepine Derivatives against Phytopathogenic Fungi

作者：Jia-Kai Zhu, Jian-Mei Gao, Cheng‐Jie Yang, Xiaofei Shang, Zhong-Min Zhao, Raymond Kobla Lawoe, Rui Zhou, Yu Sun, Xiaodan Yin, Ying‐Qian Liu · 发表于：Journal of Agricultural and Food Chemistry · 年份：2020 · DOI：10.1021/acs.jafc.9b06793 · 被引用次数：74 · 研究领域：Synthesis and bioactivity of alkaloids、Cancer therapeutics and mechanisms、Berberine and alkaloids research

Neocryptolepine is an alkaloid isolated from traditional African herbal medicine Cryptolepis sanguinolenta, and its broad spectrum of biological activities has been illuminated in past decades. In this study, neocryptolepine and its derivatives ( 1 – 49 ) were designed and synthesized from economical and readily available starting materials. Their structures were confirmed by proton nuclear magnetic resonance, carbon nuclear magnetic resonance, and mass spectrometry. The synthesized compounds were screened for their antifungal profile against six agriculturally important fungi Rhizoctonia solani, Botrytis cinerea ( B. cinerea ), Fusarium graminearum, Mycosphaerella melonis, Sclerotinia sclerotiorum, and Magnaporthe oryzae . The results of in vitro assay revealed that compounds 5, 21, 24, 35, 40, 45, and 47 presented remarkable antifungal activity against the fungi tested with EC 50 values lower than 1 μg/mL. Significantly, compound 24 displayed the most effective inhibitory potency against B. cinerea (EC 50 = 0.07 μg/mL), and the data from in vivo experiments revealed that compound 24 demonstrated comparable protective activity with the positive control boscalid. Preliminary mechanism studies indicated that compound 24 showed impressive spore germination inhibitory effectiveness and lower cytotoxicity than azoxystrobin, imparted on normal function of the cell membrane and cell wall, and arrested the normal function of the nucleus. Besides the excellent inhibitory activity aga...