Aflatoxins are secondary metabolites of the fungi Aspergillus flavus and A. parasiticus. Among them, aflatoxin B1 (AFB1) is the most frequent type in nature and the most carcinogenic for mammals. It can contaminate many kinds of food like seeds, oil, olives, milk, dairy products, corn and meat, causing acute and chronic damages to the organism, especially in the liver, being, for this reason, considered highly hepatotoxic. AFB1 is also a mixed inhibitor of the enzyme acetylcholinesterase (AChE). This fact, together with its high toxicity and carcinogenicity, turns AFB1 into a potential chemical and biological warfare agent, as well as its metabolites. In order to investigate this, we performed inedited molecular modeling studies on the interactions of AFB1 and its metabolites inside the peripheral anionic site of human AChE (HssAChE), to verify their stability, suggest the preferential ways of inhibition, and compare their behavior to each other. Our results suggest that all metabolites can be better inhibitors of HssAChE than AFB1 and that AFBO and AFM1, the most toxic and carcinogenic metabolites of AFB1, are also the most effective HssAChE inhibitors among the AFB1 metabolites. Communicated by Ramaswamy H. Sarma.

b Brazilian Army CBRN Defense Institute IDQBRN Avenida das Américas Rio de Janeiro Brazil c Natural Products Research Institute IPPN Federal University of Rio de Janeiro UFRJ Bl H Ilha do Fundão Rio de Janeiro Brazil

Department of Chemistry University of Hradec Králové Rokitanskeho Hradec Kralove Czech Republic

Department of Chemistry University of Hradec Králové Rokitanskeho Hradec Kralove Czech Republic e Faculty of Informatics and Management Center for Basic and Applied Research University of Hradec Králové Rokitanskeho 62 Hradec Králove Czech Republic

f Department of Toxicology University of Defense Trebesska Hradec Kralové Czech Republic

Laboratory of Molecular Modeling Applied to Chemical and Biological Defense Military Institute of Engineering Praça General Tibúrcio Rio de Janeiro Brazil

Laboratory of Molecular Modeling Applied to Chemical and Biological Defense Military Institute of Engineering Praça General Tibúrcio Rio de Janeiro Brazil e Faculty of Informatics and Management Center for Basic and Applied Research University of Hradec Králové Rokitanskeho 62 Hradec Králove Czech Republic

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