To identify potential human-safe insecticides against the malaria mosquito we undertook an investigation of the structure-activity relationship of aryl methylcarbamates inhibitors of acetylcholinesterase (AChE). Compounds bearing a beta-branched 2-alkoxy or 2-thioalkyl group were found to possess good selectivity for inhibition of Anopheles gambiae AChE over human AChE; up to 530-fold selectivity was achieved with carbamate 11d. A 3D QSAR model is presented that is reasonably consistent with log inhibition selectivity of 34 carbamates. Toxicity of these compounds to live Anopheles gambiae was demonstrated using both tarsal contact (filter paper) and topical application protocols.
Hartsel JA, Wong DM, Mutunga JM, Ma M, Anderson TD, Wysinski A, Islam R, Wong EA, Paulson SL, Li J, Lam PC, Totrov MM, Bloomquist JR, Carlier PR (2012) Re-engineering aryl methylcarbamates to confer high selectivity for inhibition of Anopheles gambiae versus human acetylcholinesterase Bioorganic & Medicinal Chemistry Lett22: 4593-8
Hartsel JA, Wong DM, Mutunga JM, Ma M, Anderson TD, Wysinski A, Islam R, Wong EA, Paulson SL, Li J, Lam PC, Totrov MM, Bloomquist JR, Carlier PR (2012) Bioorganic & Medicinal Chemistry Lett22: 4593-8