Affiliation:
1. University of Zagreb , Faculty of Pharmacy and Biochemistry, Department of Medicinal Chemistry , 10000 Zagreb Croatia
2. Universidade de Lisboa , Faculdade de Farmácia , 1649-004 Lisboa , Portugal
3. University of Zagreb , Faculty of Chemical Engineering and Technology 10000 Zagreb , Croatia
Abstract
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_pIGC
50/mmol L−1, acute toxicity in Pimephales promelas, the fathead minnow (TOX_FHM) expressed as Minnow LC
50/mg L−1, the acute toxicity in Daphnia magna (TOX_DM) expressed as Daphnia LC
50/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_pIGC
50/mmol L−1 (R = 0.94), also their MlogPs with Minnow_LC
50/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.
Subject
Pharmaceutical Science,Pharmacology,General Medicine
Cited by
3 articles.
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