engleski

IN SILICO ADMET STUDY OF SILDENAFIL AND ITS ANALOGUES FOUND IN HERBAL DIETARY SUPPLEMENTS – ECOTOXICITY APPROACH

Erectile dysfunction (ED) medicines are obtained outside of the official health system rivals and possibly exceeds legitimate sales. According to literature a high-risk segment of this market is occupied by adulterated food supplements. The aim of this in silico study was to evaluate phosphodiesterase 5 inhibitors (PDE5Is) including sildenafil and its analogues that were previously detected in food suplements by LC-ESI-MS/MS and to predict their toxic profile by ADMET PredictorTM (SimulationsPlus Inc., USA) in order to elucidate their impact on environment and health. ADMET-related descriptors relevant to environmental toxicity were computed using four models: the fathead minnow acute toxicity model based on lethal effects on Pimephales promelas (TOX_FHM, Minnow LC50 in mg/L), the concentration needed to inhibit 50% growth in protozoan species Tetrahymena pyriformis (TOX_ATPP, pIGC50 in mmol/L), the lethal concentration that results in death of 50% of Daphnia magna (water fleas) (TOX_DM, Daphnia LC50 in mg/L) and bioconcentration factor (BCF). The results of this in silico study revealed that investigated PDE5Is are non- biodegradable molecules and predicted scores for bioconcentration factor (BCF) were computed from 0.011 to 10.614. Toxicitis for TOX FHM expressed as Minnow LC50 wre computed from 0.147 to 15.877 mg/L, TOX_ATPP expreessed as pIGC50 from 0.945 to 1.489 mmol/L and TOX_DM exressed as Daphnia LC50 from 0.184 to 776.975 mg/L. In general, based on computed data sildenafil analogues have been revealed as more ecotoxic comparing to sildenafil itself (computed scores: BCF 1.311 ; TOX FHM Minnow LC50 2.269 mg/L ; TOX_ATTP pIGC50 0.711 mmol/L and TOX_DM Daphnia LC50 0.343).

ecotoxicity ; PDE5Is ; food supplement

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