Papyracillic acid and its derivatives as biting deterrents against Aedes aegypti (Diptera: Culicidae): structure–activity relationships

Aedes aegypti L. is the major vector of the arboviruses responsible for dengue fever, one of the most devastating human diseases. Papyracillic acid, the main phytotoxin produced by Ascochyta agropyrina var. nana, was evaluated in a preliminary screening together with other fungal phytotoxins, cyclopaldic acid, seiridin and sphaeropsidin A for their biting deterrent and larvicidal activities against Ae. aegypti. Because papyracillic acid previously showed a strong mosquito biting deterrent activity, five already known and six new derivatives were prepared in the current study to carry out a structure-activity relationship. All the compounds showed biting deterrence higher than the solvent control, ethanol. Biting deterrent activity of compounds 8, 9, 10 and 12 with biting deterrent index values of 0.76, 0.86, 0.72 and 0.74 nmol/cm2 was similar to DEET, which was 25 nmol/cm2. None of these compounds showed any larvicidal activity at the highest testing dose of 100 ppm. The bioassay results indicated that the structural feature responsible for the activity of compound 1 was probably the furanone ring. The presence of the alternative substituted cyclobutene, oxiran or substituted 4H-1,2,3-oxadiazine rings in some derivatives may be responsible for an increase in activity.