engleski

In silico prediction of ADMET properties of opium poppy alkaloids found in food

Individuals subjected to drug testing should avoid food containing poppy seeds, which are commonly used in cakes and pastries because it might be prepared with alkaloid-contaminated poppy seeds and could cause a positive opiate drug test. It is of forensic importance to assess whether and to what extent the intake of poppy seed-containing products is associated with the excretion of measurable amounts of these alkaloids and their metabolites. The study aimed to evaluate the ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties of opiate alkaloids and their safety profile using the ADMET PredictorTM to elucidate their impact on the environment and health. The obtained results revealed that the main biotransformation pathways, catalyzed by cytochrome P450 (CYP) enzymes, for phenanthrene alkaloids (morphine, codeine, thebaine, and oripavine) are O- and N-demethylation, whereas O- demethylation and further oxidation of formed catechols to the corresponding toxic o-quinones are characteristic for biotransformation pathways of papaverine and noscapine. The highest scores of ADMET_Risk were predicted for papaverine and no risk for noscapine. Likewise, the highest scores of Absn_Risk (due to physicochemical and biological properties) and CYP-Risk were also predicted for papaverine, whereas rat acute toxicity and hepatotoxicity were predicted for papaverine and oripavine. The qualitative estimation of reproductive/developmental toxicity (Repro_Tox) was predicted for papaverine and noscapine, the chromosomal aberration for morphine and oripavine, whereas androgen and estrogen receptor toxicity were predicted for all phenanthrene alkaloids. All of the investigated alkaloids are nonbiodegradable molecules with the highest ecotoxic potential of oripavine to Daphnia magna, codeine to Tetrahymena pyriformis, and papaverine to the fathead minnow (Pimephales promelas).

bioconcentration ; biotransformation ; ecotoxicity prediction test tools ; safety ; toxicity

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