Molecular modeling studies on the interactions of aflatoxin B1 and its metabolites with the peripheral anionic site of human acetylcholinesterase

Abstract

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

Keywords:

• acetylcholinesterase
• aflatoxin B1
• biological warfare agents
• chemical warfare agents
• metabolites

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors wish to thank the Military Institute of Engineering, University of Hradec Kralové (Grants no SV2103-2017 and VT2201-2018), University of Defense and the Brazilian financial agencies CNPq (Grant no 306156/2015-6), and FAPERJ (Grant no. E-02/202.961/2017). This work was also supported by the excellence project FIM.