Application of natural products as insecticide candidates: Semisynthesis and biological evaluation of some novel osthole-based esters

• Published in: Bioorganic & medicinal chemistry letters 2020-08, Vol.30 (15), p.127260, Article 127260
• Main Authors: Guo, Yong, Liu, Zhiyan, Hou, Enhua, Ma, Nannan, Gen, Yinping, Che, Pengchao, Yang, Ruige
• Format: Article
• Language: English
• Subjects: Cytotoxic activity; Hemolytic activity; Insecticidal activity; Natural product; Osthole derivative; Structure–activity relationship
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2020.127260

[Display omitted] •A series of novel osthole-based esters were synthesized through three steps.•Compounds A7, A17, A20 and A25 showed potent growth inhibitory (GI) activity.•Compound A18 displayed more promising larvicidal activity than toosendanin.•The potent derivatives A7–9, A18–21 and A25 showed very low toxicity to normal mammalian cells.•Some interesting results of structure-activity relationships were also discussed. Natural products are very important sources for the development of new pesticides. Osthole, derived from many medical plants such as Cnidium, Angelica and Citrus plants, is a naturally occurring coumarin compound. To discover the new natural products-based insecticides, thirty-one osthole-based esters containing O-acyl-hydroxylamine groups were prepared, and their structures were identified by different spectral analysis methods. Derivatives A7, A17, A20 and A25 displayed more potent growth inhibitory (GI) activity than the botanical insecticide, toosendanin. Over half of target osthole derivatives had more effective larvicidal effect on P. xylostella than toosendanin. Among all title derivatives, compound A18 displayed more pronounced larvicidal activity (LC50 = 0.64 μmol mL−1) when compared with toosendanin (LC50 = 0.94 μmol mL−1). Some interesting results of structure–activity relationships (SARs) of these osthole derivatives were also discussed. In addition, the hemolysis and cytotoxicity assays indicated that these osthole derivatives showed very low toxicity toward normal mammalian cells.