1. bookVolume 69 (2019): Issue 4 (December 2019)
Journal Details
First Published
28 Feb 2007
Publication timeframe
4 times per year
access type Open Access

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

Published Online: 21 Oct 2019
Volume & Issue: Volume 69 (2019) - Issue 4 (December 2019)
Page range: 563 - 584
Accepted: 24 Jul 2019
Journal Details
First Published
28 Feb 2007
Publication timeframe
4 times per year

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.


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