The cattle tick, Boophilus microplus (Bm), and the sandfly, Phlebotomus papatasi (Pp), are disease vectors to cattle and humans, respectively.  The purpose of this study was to characterize the inhibitor profile of acetylcholinesterases from Bm (BmAChE1) and Pp (PpAchE) compared with human and bovine AChE in order to identify divergent pharmacology that might lead to selective inhibitors.  Results indicate that BmAChE1 has uniquely low sensitivity (IC50 = 220 �M) toward tacrine, an inhibitor with nanomolar blocking potency in all previous species tested, including Pp.  In addition, BmAChE1 and PpAChE have low-nanomolar sensitivity to a variety of carbamate anticholinesterases.  One experimental compound, 2-((2-ethylbutyl)thio)phenyl methylcarbamate, possesses > 300-fold selectivity for BmAChE1 and PpAChE over human AChE, and a mouse oral LD50 of > 1500 mg/kg, thus providing an excellent new lead for vector control.

Design of novel carbamate insecticides with superior selectivity for the control of cattle tick (<i>Boophilus microplus</i>) and sandfly (<i>Phlebotomus papatasi</i>) populations

244th National Meeting (2012)

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Design of novel carbamate insecticides with superior selectivity for the control of cattle tick (Boophilus microplus) and sandfly (Phlebotomus papatasi) populations