Interpretation of honeybees contact toxicity associated to acetylcholinesterase inhibitors.
The widespread use of different pesticides generates adverse effects on non target organisms like honeybees. Organophosphorous and carbamates kill honeybees through the inactivation of acetylcholinesterase (AChE), thereby interfering with nerve signaling and function. For this class of pesticides, it is fundamental to understand the relationship between their structures and the contact toxicity for honeybees. A Quantitative Structure-Activity Relationship (QSAR) study was carried out on 45 derivatives by a genetic algorithm approach starting from more than 2500 descriptors. In parallel, a new 3D model of AChE associated to honeybees was defined. Physicochemical properties of the receptor and docking studies of the derivatives allow understanding the meaningful of three descriptors and the implication of several amino acids in the overall toxicity of the pesticides.
Centre d'Etudes et de Recherche sur le Médicament de Normandie, UPRES EA-4258, INC3M FR CNRS 3038, Université de Caen Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Boulevard Becquerel, 14032 Caen Cedex, France.
Fabienne
F
Dulin
Centre d'Etudes et de Recherche sur le Médicament de Normandie, UPRES EA-4258, INC3M FR CNRS 3038, Université de Caen Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Boulevard Becquerel, 14032 Caen Cedex, France.
Marie-Pierre
MP
Halm-Lemeille
Centre d'Etudes et de Recherche sur le Médicament de Normandie, UPRES EA-4258, INC3M FR CNRS 3038, Université de Caen Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Boulevard Becquerel, 14032 Caen Cedex, France.
Sylvain
S
Lozano
Centre d'Etudes et de Recherche sur le Médicament de Normandie, UPRES EA-4258, INC3M FR CNRS 3038, Université de Caen Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Boulevard Becquerel, 14032 Caen Cedex, France.
Alban
A
Lepailleur
Centre d'Etudes et de Recherche sur le Médicament de Normandie, UPRES EA-4258, INC3M FR CNRS 3038, Université de Caen Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Boulevard Becquerel, 14032 Caen Cedex, France.
Jana
J
Sopkova-de Oliveira Santos
Centre d'Etudes et de Recherche sur le Médicament de Normandie, UPRES EA-4258, INC3M FR CNRS 3038, Université de Caen Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Boulevard Becquerel, 14032 Caen Cedex, France.
Sylvain
S
Rault
Centre d'Etudes et de Recherche sur le Médicament de Normandie, UPRES EA-4258, INC3M FR CNRS 3038, Université de Caen Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Boulevard Becquerel, 14032 Caen Cedex, France. Electronic address: ronan.bureau@unicaen.fr.
Ronan
R
Bureau
D000110:Acetylcholinesterase / Q000378:metabolism; D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D001516:Bees; D002219:Carbamates / Q000737:chemistry / Q000633:toxicity; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000633:toxicity*; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000633:toxicity; D021281:Quantitative Structure-Activity Relationship
D002219:Carbamates; D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D000110:Acetylcholinesterase