PMID- 22989775
OWN - NLM
STAT- MEDLINE
DCOM- 20130528
LR  - 20211021
IS  - 1872-7786 (Electronic)
IS  - 0009-2797 (Print)
IS  - 0009-2797 (Linking)
VI  - 203
IP  - 1
DP  - 2013 Mar 25
TI  - Aryl methylcarbamates: potency and selectivity towards wild-type and 
      carbamate-insensitive (G119S) Anopheles gambiae acetylcholinesterase, and 
      toxicity to G3 strain An. gambiae.
PG  - 314-8
LID - S0009-2797(12)00166-4 [pii]
LID - 10.1016/j.cbi.2012.09.001 [doi]
AB  - New carbamates that are highly selective for inhibition of Anopheles gambiae 
      acetylcholinesterase (AChE) over the human enzyme might be useful in continuing 
      efforts to limit malaria transmission. In this report we assessed 34 synthesized 
      and commercial carbamates for their selectivity to inhibit the AChEs found in 
      carbamate-susceptible (G3) and carbamate-resistant (Akron) An. gambiae, relative 
      to human AChE. Excellent correspondence is seen between inhibition potencies 
      measured with carbamate-susceptible mosquito homogenate and purified recombinant 
      wild-type (WT) An. gambiae AChE (AgAChE). Similarly, excellent correspondence is 
      seen between inhibition potencies measured with carbamate-resistant mosquito 
      homogenate and purified recombinant G119S AgAChE, consistent with our earlier 
      finding that the Akron strain carries the G119S mutation. Although high (100- to 
      500-fold) WT An. gambiae vs human selectivity is observed for several compounds, 
      none of the carbamates tested potently inhibits the G119S mutant enzyme. Finally, 
      we describe a predictive model for WT An. gambiae tarsal contact toxicity of the 
      carbamates that relies on inhibition potency, molecular volume, and polar surface 
      area.
CI  - Copyright (c) 2012 Elsevier Ireland Ltd. All rights reserved.
FAU - Wong, Dawn M
AU  - Wong DM
AD  - Department of Chemistry, Virginia Tech, Blacksburg, VA 240161, USA.
FAU - Li, Jianyong
AU  - Li J
FAU - Lam, Polo C H
AU  - Lam PC
FAU - Hartsel, Joshua A
AU  - Hartsel JA
FAU - Mutunga, James M
AU  - Mutunga JM
FAU - Totrov, Maxim
AU  - Totrov M
FAU - Bloomquist, Jeffrey R
AU  - Bloomquist JR
FAU - Carlier, Paul R
AU  - Carlier PR
LA  - eng
GR  - R01 AI082581/AI/NIAID NIH HHS/United States
GR  - AI082581/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120916
PL  - Ireland
TA  - Chem Biol Interact
JT  - Chemico-biological interactions
JID - 0227276
RN  - 0 (Carbamates)
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Insect Proteins)
RN  - 0 (Insecticides)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.1.1.7 (Acetylcholinesterase)
SB  - IM
MH  - Acetylcholinesterase/*genetics/*metabolism
MH  - Amino Acid Substitution
MH  - Animals
MH  - Anopheles/*drug effects/*enzymology/genetics
MH  - Carbamates/chemistry/*pharmacology
MH  - Cholinesterase Inhibitors/chemistry/pharmacology
MH  - Drug Evaluation, Preclinical
MH  - Humans
MH  - Insect Proteins/antagonists & inhibitors/genetics
MH  - Insecticide Resistance/genetics
MH  - Insecticides/chemistry/pharmacology
MH  - Mutagenesis, Site-Directed
MH  - Recombinant Proteins/antagonists & inhibitors/genetics
PMC - PMC3578073
MID - NIHMS408386
EDAT- 2012/09/20 06:00
MHDA- 2013/05/29 06:00
PMCR- 2014/03/25
CRDT- 2012/09/20 06:00
PHST- 2012/08/03 00:00 [received]
PHST- 2012/09/05 00:00 [revised]
PHST- 2012/09/06 00:00 [accepted]
PHST- 2012/09/20 06:00 [entrez]
PHST- 2012/09/20 06:00 [pubmed]
PHST- 2013/05/29 06:00 [medline]
PHST- 2014/03/25 00:00 [pmc-release]
AID - S0009-2797(12)00166-4 [pii]
AID - 10.1016/j.cbi.2012.09.001 [doi]
PST - ppublish
SO  - Chem Biol Interact. 2013 Mar 25;203(1):314-8. doi: 10.1016/j.cbi.2012.09.001. 
      Epub 2012 Sep 16.