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).