RESUMO
BACKGROUND: Previous work has demonstrated that piperonyl butoxide (PBO) not only inhibits microsomal oxidases but also resistance-associated esterases. The ability to inhibit both major metabolic resistance enzymes makes it an ideal synergist to enhance xenobiotics but negates the ability to differentiate which enzyme group is responsible for conferring resistance. RESULTS: This study examines an analogue that retains the ability to inhibit esterases but is restricted in its ability to act on microsomal oxidases, thus allowing an informed decision on resistance enzymes to be made when used in conjunction with the parent molecule. CONCLUSION: Using examples of resistant insects with well-characterised resistance mechanisms, a combination of PBO and analogue allows identification of the metabolic mechanism responsible for conferring resistance. The relative potency of PBO as both an esterase inhibitor and an oxidase inhibitor is also discussed.
Assuntos
Inibidores Enzimáticos/farmacologia , Esterases/antagonistas & inibidores , Proteínas de Insetos/antagonistas & inibidores , Resistência a Inseticidas , Sinergistas de Praguicidas/farmacologia , Butóxido de Piperonila/farmacologia , Animais , Inibidores Enzimáticos/síntese química , Esterases/metabolismo , Hemípteros/efeitos dos fármacos , Hemípteros/enzimologia , Proteínas de Insetos/metabolismo , Sinergistas de Praguicidas/síntese química , Butóxido de Piperonila/análogos & derivados , Butóxido de Piperonila/síntese químicaRESUMO
Previous work demonstrated that a commercial formulation of piperonyl butoxide (PBO) did inhibit the activity of some plant proteolytic enzymes. In this paper, the effect of pure PBO and nine pure PBO homologues (PBOH) appropriately synthesized toward bromelain and papain was studied in hydrocarbon solution using the bis(2-ethylhexyl)sodium sulfosuccinate (AOT) reverse micellar system. This study establishes that the majority of these compounds show, in vitro, interesting protease inhibition activities. The benzodioxole and dihydrobenzofuran structures, in particular, 5-[2-(2-butoxyethoxy)ethoxymethyl]-benzo[1,3]dioxole (EN 1-40) and 6-[2-(2-butoxyethoxy)ethoxymethyl]-5-propyl-2,3-dihydrobenzofuran (EN 16-5), respectively, appear to be responsible for protease inhibition. Measures of octanol/water partition coefficients on PBO and PBOH have demonstrated that water solubility plays a fundamental role in the expression of protease inhibition activity.