Natural Product-Based Pesticide Discovery: Design, Synthesis and Bioactivity Studies of N-Amino-Maleimide Derivatives.

Xiangmin Song,Ranfeng Sun,Chunjuan Liu,Hao Zhang,Peiqi Chen

doi:10.3390/molecules23071521

Xiangmin Song, Ranfeng Sun + Show 3 more

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https://doi.org/10.3390/molecules23071521

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Abstract

Natural products are an important source of pesticide discovery. A series of N-amino-maleimide derivatives containing hydrazone group were designed and synthesized based on the structure of linderone and methyllinderone which were isolated from Lindera erythrocarpa Makino. According to the bioassay results, compounds 2 and 3 showed 60% inhibition against mosquito (Culex pipiens pallens) at 0.25 µg·mL−1. Furthermore, the results of antifungal tests indicated that most compounds exhibited much better antifungal activities against fourteen phytopathogenic fungi than linderone and methyllinderone and some compounds exhibited better antifungal activities than commercial fungicides (carbendazim and chlorothalonil) at 50 µg·mL−1. In particular, compound 12 exhibited broad-spectrum fungicidal activity (>50% inhibitory activities against 11 phytopathogenic fungi) and compounds 12 and 14 displayed 60.6% and 47.9% inhibitory activity against Rhizoctonia cerealis at 12.5 µg·mL−1 respectively. Furthermore, compound 17 was synthesized, which lacks N-substituent at maleimide and its poor antifungal activity against Sclerotinia sclerotiorum and Rhizoctonia cerealis at 50 µg·mL−1 showed that the backbone structure of N-amino-maleimide derivatives containing hydrazone group was important to the antifungal activity.

Highlights

Chitin is a unique component of the fungal cell wall and shells of crustaceans, but it is absent in vertebrates, mammals, and humans [1]
Methyllinderone (A) and linderone (B), which were classic inhibitors of chitin synthetase (Figure 1), were isolated from Lindera erythocarpa Makino (Lauraceae) and exhibited inhibitory activity against chitin synthase 2 (CaCHS2p) with IC50 value of 23.3, 21.4 μg·mL−1 respectively, which was better than polyoxin D (70.0 μg·mL−1 ) and nikkomycin Z (176.0 μg·mL−1 ) [3]
Different aryl-substituted unsaturated ketones, which were synthesized according to the literature

Summary

Introduction

Chitin is a unique component of the fungal cell wall and shells of crustaceans, but it is absent in vertebrates, mammals, and humans [1]. Chitin synthase is an attractive molecular target for developing fungicides and insecticides. Lindera species (Lauraceae) have rich chemical compositions and pharmacological activities [2]. Methyllinderone (A) and linderone (B), which were classic inhibitors of chitin synthetase (Figure 1), were isolated from Lindera erythocarpa Makino (Lauraceae) and exhibited inhibitory activity against chitin synthase 2 (CaCHS2p) with IC50 value of 23.3, 21.4 μg·mL−1 respectively, which was better than polyoxin D (70.0 μg·mL−1 ) and nikkomycin Z (176.0 μg·mL−1 ) [3]. In 2015, Seok-Hee Lee et al reported that methyllinderone (A) and methyllucidone (C) (Figure 1) exhibited juvenile hormone antagonistic activity against Aedes aegypti [4]. Sheng-Yang Wang et al reported that linderone (D), methyllinderone (A), lucidone (E) and methyllucidone (C) (Figure 1) displayed good anti-inflammatory activity [5]

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