Dillapiol Derivatives as Synergists: Structure-Activity Relationship Analysis

The synergistic activity of synthetic derivatives of dillapiol, a naturally occurring synergist, was assessed in combination with the phototoxin alpha-terthienyl against mosquito larvae (Aedes atropalpus). The synergistic activity varied between 0.9 and 2.4 with alpha-terthienyl in a 1:5 insecticide/synergist ratio, while none of the derivatives was toxic alone at the highest concentrations used. Naturally occurring dillapiol remained one of the most active compounds. The role of the lipophilicity, expressed as the logarithm of the octanol:water partition coefficient, Log P, was assessed in a quantitative structure-activity relationship analysis. A characteristic parabolic relationship between toxicity (1/LC50) and lipophilicity was found to be significant: Log (1/LC50) = 1.58 Log P - 0.24 Log P2 - 6.47 (P < 0.001, r2 = 0.94, n = 8). A linear correlation between the toxicity of the alpha-terthienyl/synergist combination and the retention of alpha-terthienyl in the larvae was also found to be significant (P < 0.001, with r = 0.865): Log (1/LC50) = 0.236 Log (alpha-T conc.) - 5.5.