<abstract xmlns="http://www.w3.org/1999/xhtml">The impact of the selected entactogens and their <italic>o</italic>-quinone metabolites on the environment was explored in QSAR studies by the use of predicted molecular descriptors, ADMET properties and environmental toxicity parameters, <italic>i.e.</italic>, acute toxicity in <italic>Tetrahymena pyriformis</italic> (TOX_ATTP) expressed as <italic>Th_pyr_pIGC</italic>50/mmol L−1, acute toxicity in <italic>Pimephales promelas</italic>, the fathead minnow (TOX_FHM) expressed as <italic>Minnow LC</italic>50/mg L−1, the acute toxicity in <italic>Daphnia magna</italic> (TOX_DM) expressed as <italic>Daphnia LC</italic>50/mg L−1 and bioconcentration factor (BCF).The formation of corresponding <italic>o</italic>-quinones <italic>via</italic> benzo-dioxo-lone ring, <italic>O</italic>-demethylenation was predicted as the main metabolic pathway for all entactogens except for 1-(2,2-difluorobenzo[<italic>d</italic>][1,3]dioxol-5-yl)propan-2-amine (DiFMDA). The least favourable ADMET profile was revealed for <italic>N</italic>-(1-(benzo[<italic>d</italic>][1,3]dioxol-5-yl)propan-2-yl)-<italic>O-</italic>methylhydroxylamine (MDMEO).QSAR studies revealed significant linear correlations between <italic>MlogP</italic> of entactogens and <italic>MlogP</italic> of <italic>o</italic>-quinone metabolites (<italic>R</italic> = 0.99), and <italic>Th_pyr_pIGC</italic>50/mmol L−1 (<italic>R</italic> = 0.94), also their <italic>MlogP</italic>s with <italic>Minnow_LC</italic>50/mg L−1 (<italic>R</italic> = 0.80 and <italic>R</italic> = 0.78), BCF (<italic>R</italic> = 0.86 and <italic>R</italic> = 0.82) and percentage of <italic>o</italic>-quinones’ yields (<italic>R</italic> = 0.73 and <italic>R</italic> = 0.80). Entactogens were predicted as non-biodegradable molecules, whereas the majority of their <italic>o</italic>-quinones were biodegradable.</abstract>

The impact of the selected entactogens and their o-quinone metabolites on the environment was explored in QSAR studies by the use of predicted molecular descriptors, ADMET properties and environmental toxicity parameters, i.e., acute toxicity in Tetrahymena pyriformis (TOX_ATTP) expressed as Th_pyr_pIGC50/mmol L−1, acute toxicity in Pimephales promelas, the fathead minnow (TOX_FHM) expressed as Minnow LC50/mg L−1, the acute toxicity in Daphnia magna (TOX_DM) expressed as Daphnia LC50/mg L−1 and bioconcentration factor (BCF).The formation of corresponding o-quinones via benzo-dioxo-lone ring, O-demethylenation was predicted as the main metabolic pathway for all entactogens except for 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)propan-2-amine (DiFMDA). The least favourable ADMET profile was revealed for N-(1-(benzo[d][1,3]dioxol-5-yl)propan-2-yl)-O-methylhydroxylamine (MDMEO).QSAR studies revealed significant linear correlations between MlogP of entactogens and MlogP of o-quinone metabolites (R = 0.99), and Th_pyr_pIGC50/mmol L−1 (R = 0.94), also their MlogPs with Minnow_LC50/mg L−1 (R = 0.80 and R = 0.78), BCF (R = 0.86 and R = 0.82) and percentage of o-quinones’ yields (R = 0.73 and R = 0.80). Entactogens were predicted as non-biodegradable molecules, whereas the majority of their o-quinones were biodegradable.

Evaluation of phenylethylamine type entactogens and their metabolites relevant to ecotoxicology – a QSAR study

Faculty of Pharmacy and Biochemistry, Department of Medicinal Chemistry

Faculty of Chemical Engineering and Technology

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

The impact of the selected entactogens and their o-quinone metabolites on the environment was explored in QSAR studies by the use of predicted molecular...

Evaluation of phenylethylamine type entactogens and their metabolites relevant to ecotoxicology – a QSAR study

Published Online: Oct 21, 2019

Page range: 563 - 584

Accepted: Jul 24, 2019

DOI: https://doi.org/10.2478/acph-2019-0038

Keywords
entactogens, ecstasy, ADMET, CYP metabolism, ecotoxicity, QSAR

© 2019 Milena Jadrijević-Mladar Takač et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Evaluation of phenylethylamine type entactogens and their metabolites relevant to ecotoxicology – a QSAR study

Published Online: Oct 21, 2019

Page range: 563 - 584

Accepted: Jul 24, 2019

DOI: https://doi.org/10.2478/acph-2019-0038

Keywordsentactogens, ecstasy, ADMET, CYP metabolism, ecotoxicity, QSAR

© 2019 Milena Jadrijević-Mladar Takač et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
entactogens, ecstasy, ADMET, CYP metabolism, ecotoxicity, QSAR