As our ongoing work on research of natural-product-based insecticidal agents, eighteen podophyllotoxin analogues with diverse chemical structures were evaluated for their insecticidal activities against the pre-fourth-instar larvae of Athetis dissimilis Hampson in vivo at the concentration of 1 mg/mL. Among all the reported analogues, compounds 6, 8, 12, 13, 15 and 17 showed more potent insecticidal activities than matrine, quinine and toosendanin, three commercial plant secondary metabolites. 2′,6′-Dichloropodophyllotoxin (8) and 2′,6′-dichloroepipodophyllotoxin (13) exhibited the most pronounced and promising insecticidal activity with the final corrected mortality rates of greatly 60%. This suggested that variation of chemical structures in the podophyllotoxin skeleton conspicuously has effect on the insecticidal activity profiles of podophyllotoxin analogues. Moreover, SAR revealed that the substituents and configuration were critical for their insecticidal activities. The results may be useful in guiding further design and structural modification of podophyllotoxins in the development of potential novel insecticidal agents.
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