engleski

Evaluation of Entactogens of Phenylethylamine Type and their Metabolites Relevant to Ecotoxicity – a QSAR Study

The impact of selected entactogens and their o-quinone metabolites on environment was explored in QSAR studies by use of predicted molecular decriptors, ADMET properties and environmental toxicity parameters, i.e., acute toxicity in Tetrahymena pyriformis (TOX_ATTP) expressed as Th_pyr_pIGC50/mmolL-1, acute toxicity in Pimephales promelas, the fathead minnow (TOX_FHM) expressed as Minnow LC50/mgL-1, the acute toxicity in Daphnia magna (TOX_DM) expressed as Daphnia LC50/mgL-1 and bioconcentration factor (BCF). The formation of corresponding o-quinones via benzo-dioxolone ring O-demetylenation 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-methylhydroxyl-amine (MDMEO). QSAR studies revealed significant linear correlations between MlogP of entactogens and MlogP o-quinone metabolites (R=0.99), and Th_pyr_pIGC50/mmolL-1 (R=0.94 ), also their MlogPs with Minnow_LC50/mgL-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 while majority of their o-quinones were biodegradable.

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

Koautori na radu su studenti Farmaceutskog fakulteta Sveučilišta u Lisabonu (Portugal) koji je boravio na Sveučilištu u Zagrebu u okviru ERASMUS+ i Fakulteta kemijskog inženjerstva i tehnologije Sveučilišta u Zagrebu (Hrvatska).