Exploration of binding interaction of aflatoxin metabolite with p53 gene protein, enzymes CYP3A4 in carcinogenesis and its prevention: An in silico study

Abstract

The foodborne pathogens and their toxic metabolites contaminants are global threat to the human and animal health. Aflatoxin, is one of the fungal carcinogen produced by foodborne pathogen Aspergillus. It metabolizes by cytochrome enzymes and interacts with DNA and p53 gene protein causes cancers in human and animals. In this study, metabolic carcinogenic interactions of aflatoxin, its epoxy metabolite and prevention have explored. This study is stated that epoxide metabolite of aflatoxin more significantly interacts with cytochrome enzyme CYP3A4, human serum protein, p53 gene protein and B-DNA. The observed interacting binding energy of CYP3A4 enzyme was −7.80 kcal/mol and it was bonded with hydrogen bond.Human serum albumin is also observed to be interacted significantly with the epoxide metabolite of aflatoxin through A:HIS146:CA – :UNK1:O22, bond length 2.8958, the binding energy −7.01 kcal/mol and inhibition constant 7.33 uM. The binding interaction of metabolite with B-DNA were A:DA5:H7 – :UNK1:O8, 1.94187, −5.23 kcal/mol and 145.62 µM. The metabolizing enzyme CYP3A4 is inhibited by ketoconazole with less efficiently than betulinic acid and followed by Urolithin b and thymoquinone. Urolithin b a constituent of pomegranate and thymoquinone found in black seed could be a preventive step for the management of aflatoxin mediated toxicity and carcinogenesis. Therefore, in vivo and in vitro laboratory experimentation on inhibition of CYP3A4 enzymes involved in metabolism and epoxidation of toxin by betulinic acid will be further helpful for the aflatoxins detoxification and cancer prevention.