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

Neocryptolepine is an alkaloid isolated from traditional African herbal medicine Cryptolepis sanguinolenta and its broad spectrum of biological activities have 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 1H NMR, 13C NMR and MS. The synthesized compounds were screened for their antifungal profile against six agriculturally important fungi Rhizoctonia solani, Botrytis cinerea, Fusarium graminearum, Mycosphaerlla 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 EC50 values lower than 1 μg/mL. Significantly, compound 24 displayed the most effective inhibitory potency against Botrytis cinerea (EC50 = 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, lower cytotoxicity than azoxystrobin, imparted on normal function of cell membrane, cell wall and arrested the normal function of the nucleus. Besides, the excellent inhibitory activity against agriculturally important phytopathogenic fungi tested, the designed assemblage possesses several benefits with a high-profile of variation in synthesized molecules, the ease of synthesis and good cost-effectiveness of commercially available synthetic reagents, all of these have highlighted the potential worth of compound 24 as a new and highly efficient agricultural fungicide.