Lim_2024_Int.J.Mol.Sci_25_13291

Exposure to tamoxifen can exert effects on the human liver, and esterases process prodrugs such as antibiotics and convert them to less toxic metabolites. In this study, the porcine liver esterase (PLE)-inhibitory activity of tamoxifen has been investigated. PLE showed inhibition of a PLE isoenzyme (PLE5). In addition, avenanthramides, which have a similar structure to that of tamoxifen, have been used to determine the PLE-inhibitory effect. Among the avenanthramide derivatives, avenanthramide B has been shown to inhibit PLE. Avenanthramide B interacts with Lys284 of PLE, whereas avenanthramide A and C counteract with Lys284. Avenanthramide B has shown a similar inhibitory effect to that of tamoxifen. Given that avenanthramide B can modulate the action of PLE, it can be used in pharmaceutical and industrial applications for modulating the effects of PLE. Based on superimposed structures between PLE and human liver esterase, the impact of tamoxifen use in humans is discussed. In addition, this study can serve as a fundamental basis for future investigations regarding the potential risk of tamoxifen and other drugs. Thus, this study presents an insight into the comparison of structurally similar tamoxifen and avenanthramides on liver esterases, which can have implications for the pharmaceutical and agricultural industries.