Biting deterrent activity of a deet analog, two DEPA analogs, and SS220 applied topically to human volunteers compared with deet against three species of blood-feeding flies.

An earlier in vitro screening of N,N-diethyl-3-methylbenzamide (Deet) and N,N-diethylphenylacetamide (DEPA) analogs showed that two DEPA analogs, N,N-diethyl(3-bromophenyl) acetamide and N,N-diethyl[(alpha,alpha,alpha-trifluoro-m-tolyl)]acetamide, and one Deet analog, N,N,diethyl[3-(trifluoromethyl)]benzamide, had biting-deterrent activities that were superior to Deet against Aedes aegypti (L.) and Anopheles stephensi Liston. In the current study, the three analogs and (1S,2'S)-methylpiperidinyl-3-cyclohexene-1-carboxamide (SS220) were applied topically to the skin of human volunteers at 24 nmol compound/cm2 skin and compared with the activity of Deet at the same dose against biting by Ae. aegypti, An. stephensi, and Phlebotomus papatasi Scopoli females. SS220 proved to be as effective as Deet against Ae. aegypti and P. papatasi but more effective than Deet against An. stephensi. Contrary to the earlier in vitro tests, results with humans (in vivo testing) showed that neither of the DEPA analogs nor the Deet analog performed more effectively than Deet against the insects. The in vivo results showed that the analogs were not sufficiently effective to warrant further development. Notably, in vivo and in vitro methods used in discovery of personal protection chemicals for human use against blood-feeding flies can both be effective discriminating tools, but results obtained with the respective methods may not always agree. Ultimately, we surmise that in vivo testing methods with humans must be used to discriminate among compounds that superficially seem effective when screened using an in vitro method.