Diapause hormone and its analogs terminate pupal diapause in Helicoverpa zea when injected, but if such agents are to be used as effective diapause disruptors it will be essential to develop simple techniques for administering active compounds that can exert their effect by penetrating the insect epidermis. In the current study, we used two molecules previously shown to have high diapause-terminating activity as lead molecules to rationally design and synthesize new amphiphilic compounds with modified hydrophobic components. An assay for diapause termination identified 13 active compounds with EC50\'s ranging from 0.9 to 46.0 pmol per pupa. Three compounds, Decyl-1963, Dodecyl-1967, and Heptyl-1965, selected from the 13 compounds most active in breaking diapause following injection, also successfully prevented newly-formed pupae from entering diapause when applied topically. These compounds feature straight-chain, aliphatic hydrocarbons from 7 to 12 carbons in length; DH analogs with either a short-chain length of 4 or an aromatic phenethyl group failed to act topically. Compared to a high diapause incidence of 80-90% in controls, diapause incidence in pupae receiving a 10 nmole topical application of Decyl-1963, Dodecyl-1967, or Heptyl-1965 dropped to 30-45%. Decyl-1963 and Dodecyl-1967 also remained effective when topically applied at the 1 nmole level. These results suggest the feasibility of developing DH
agonists that can be applied topically and suggest the identity of new lead molecules for development of additional topically-active DH analogs. The ability to penetrate the insect epidermis and/or midgut lining is critical if such agents are to be considered for future use as pest management tools.