Synthesis and biological activities of two camptothecin derivatives against Spodoptera exigua

Abstract

Camptothecin (CPT), a natural alkaloid isolated from Camptotheca acuminata Decne, is found to show potential insecticidal activities with unique action mechanisms by targeting at DnA-topoisomease I (Top1) complex and inducing cell apoptosis. To improve the efficacy against insect pests, two camptothecin (CPT) derivatives were synthesized through introducing two functional groups, 2-nitroaminoimidazoline and 1-chloro-2-isocyanatoethane by esterification reaction. The insecticidal activities of these two derivatives were evaluated at contact toxicity, cytotoxicity and topoisomerase I (Top1) inhibitory activities comparing with CPT and hydroxyl-camptothecin (HCPT). Results showed that compound a, synthesized by introducing 2-nitroaminoimidazoline to CPT, apparently increased contact toxicity to the third larvae of beet armyworm, Spodoptera exigua, and cytotoxicity to IOZCAS-Spex-II cells isolated from S. exigua. However, the inhibition on DNA relaxation activity of Top1 was reduced to less than 5 percentage even at high concentrations (50 and 100 μM). For introducing 1-chloro-2-isocyanatoethane to HCPT, the contact toxicity, cytotoxicity and Top1 inhibitory activity of synthesized compound b were increased significantly compared to CPT and HCPT. These results suggested that both synthesized compounds possessed high efficacy against S. exigua by targeting at Top1 (compound b) or novel mechanism of action (compound a).Plant secondary metabolites have a long history as a source of, and inspiration for, novel insect control agent. Examples include pyrethrum, nicotine, rotenone, which were used directly for pest control and/or as the lead compounds to develop insecticides. Camptothecin (CPT, 1, Fig. 1) is a naturally occurring alkaloid believed to serve as a defense against insect herbivores 1,2 . In China, the farmer had applied historically the crude extract of C. acuminata to control insect pests 3 . Recently, much interest has been focused on CPT due to its bioactivities to some important pest insects and unique action mechanisms by targeting at DNA and topoisomerase I (Top1) complex and inducing cell apoptosis 4-6 .Several studies have demonstrated that CPT shows toxic effects on fruit flies (Drosophila melanogaster Meigen) 7 , house flies (Musca domestica Linnaeus) 2 , and several important agricultural pest species including Spodoptera exigua Hübner 3 , Nilaparvata lugens Stål, Brevicoryne brassicae Linnaeus, and Chilo suppressalis Walker 8 . Interestingly, Sun et al. evaluated CPT synergistic effects on Bacillus thuringiensis (Bt) var. kurstaki and nucleopolyhedroviruses against Trichoplusia ni (Hübner) and S. exigua 9 . Results showed that CPT enhanced significantly the toxicity of Bt var. kurstaki to S. exigua and T. ni, and the infectivity of Autographa californica (Speyer) multinucleocapsid nucleopolyhedrovirus (AcMNPV) and S. exigua nucleopolyhedrovirus (SeMNPV). CPT and its derivatives, hydroxylcamptothecin (HCPT, 2, Fig. 1) could induce apoptosis in insect cell lines, such as IOZCAS-Spex-II (established fr...

Growth inhibition of Spodoptera frugiperda larvae by camptothecin correlates with alteration of the structures and gene expression profiles of the midgut

“…In fact, many existing insecticides are derivatives of plant metabolites. For example, pyrethrum and nicotine are used as botanical pesticides for pest control for decades [10]. In recent years, the effect of plant secondary metabolites against S. frugiperda has been investigated.…”

1H NMR‐based metabonomic evaluation of the pesticides camptothecin and matrine against larvae of Spodoptera litura

“…22 CPT derivatives are highly efficient against Spodoptera exigua, probably by acting on Topo 1. 36 Similarly, as a natural alkaloid, MAT is commonly used to treat diseases such as viral hepatitis, cancer, viral hepatitis, and inflammation. 9 Also, MAT is an important botanical pesticide due to its broad-spectrum insecticidal activities and environmental friendliness.…”

“…For example, CPT has been reported to cause epithelial cell apoptosis in the midgut and thus exert strong toxicity towards S. litura 22 . CPT derivatives are highly efficient against Spodoptera exigua , probably by acting on Topo 1 36 . Similarly, as a natural alkaloid, MAT is commonly used to treat diseases such as viral hepatitis, cancer, viral hepatitis, and inflammation 9 .…”

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