To control the malaria vector, Anopheles gambiae (Ag), we have developed several phenyl substituted N-methylcarbamates that display a high degree of selectivity (>1000-fold) over human acetylcholinesterase (AChE). Selectivity data was originally obtained using EtOH as the solvent during the screening process. Re-screening of these carbamates in the presence of 0.1% DMSO (v/v) resulted in higher IC50s for AgAChE, thus reducing the AgAChE-selectivity by at least 10-fold. However, the presence of DMSO did not antagonize the inhibition of human, Drosophila melanogaster, or Musca domestica AChE. No antagonism of inhibition was observed toward any species studied (including AgAChE) with non-selective carbamates or when EtOH was used as a solvent. Molecular models provide an explanation for antagonism of inhibition when DMSO is present, and the implications for high throughput screening will be discussed.

Experimental evidence for allosteric solvent effects between mosquito-selective carbamates and the malaria vector, A<i>nopheles gambiae</i>

239th National Meeting (2010)

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Experimental evidence for allosteric solvent effects between mosquito-selective carbamates and the malaria vector, Anopheles gambiae