title: Computational evidence for the reactivation process of human acetylcholinesterase inhibited by carbamates.
abstract: Acetylcholinesterase (AChE) is responsible for hydrolysis of acetylcholine (ACh), a function, which if disrupted, leads to cholinergic syndrome. Carbamates (CB) and organophosphorus compounds (OP) are AChE inhibitors, toxic and capable of causing severe poisoning or death to exposed individuals. The AChE reactivation is considered the main function of the oximes. In case of poisoning by CB, there is no consistent data in the literature for an oxime reactivation mechanism. In this work, we evaluated the affinity and reactivity of oximes with activity already reported against AChE inhibited by the OP chemical warfare agent ciclosarin, with MmAChE and HsAChE active sites inhibited by the CB pesticide carbofuran. Thus, our theoretical data indicate that HLO-7, BI-6 and K005 compounds may be promising reactivators of AChE inhibited by carbofuran.
authors.forename: Karina Silvia
authors.initials: KS
authors.lastname: Matos
authors.forename: Elaine F F
authors.initials: EF
authors.lastname: da Cunha
authors.forename: Ruben
authors.initials: R
authors.lastname: Abagyan
authors.affiliation: Chemistry Department, Federal University of Lavras, Campus Universitario, 3037, 37200-000, Lavras, MG, Brazil. teo@dqi.ufla.br.
authors.forename: Teodorico C
authors.initials: TC
authors.lastname: Ramalho
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002219:Carbamates / Q000737:chemistry / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects*; D006801:Humans; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D010091:Oximes / Q000737:chemistry / Q000494:pharmacology*; D016415:Sequence Alignment
chemical_list: D002219:Carbamates; D002800:Cholinesterase Inhibitors; D010091:Oximes; D000110:Acetylcholinesterase