Naslov
The Influence of In Vivo Metabolic Modifications on ADMET Properties of Green Tea Catechins-In Silico Analysis
(He Influence of In Vivo Metabolic Modifications on ADMET Properties of Green Tea Catechins-In Silico Analysis)

Autori
Matić, Sara ; Jadrijević-Mladar Takač, Milena ; Barbarić, Monika ; Lučić, Bono ; Gall Trošelj, Koraljka ; Stepanić, Višnja

Izvornik
Journal of pharmaceutical sciences (0022-3549) 107 (2018), 11; 2957-2964

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
albumin ; computational ADMET ; conjugates ; gastroPlus modeling ; molecular modeling

Sažetak
The health effects of green tea are associated with catechins: (-)-epigallocatechin-3-O-gallate (EGCG), (-)-epigallocatechin, (-)-epicatechin-3- O-gallate, and (-)-epicatechin. An understanding of compound absorption, distribution, metabolism, excretion, and toxicity characteristics is essential for explaining its biological activities. Herein, absorption, distribution, metabolism, excretion, and toxicity properties of in vivo detected metabolites of green tea catechins (GTCs) have been analyzed in silico. The influence of metabolic transformations on absorption, distribution, metabolism, and excretion profiles of GTCs corresponds to the effects of size, charge, and lipophilicity, as already observed for other small molecules. Mutagenic, carcinogenic, or liver toxic effects were predicted only for a few metabolites. Similar to galloylated GTCs EGCG and (--)-epicatechin-3-O- gallate, the sulfo-conjugates were predicted to bind at the warfarin binding site. The low free plasma concentration of these derivatives may be consequential to their serum albumin binding. The activity cliff detected for methylated conjugates of EGCG indicates that GTCs' pro- oxidative activity in bound state comes primarily from free hydroxyl groups of the pyrogallol ring B.

Izvorni jezik
Engleski

Znanstvena područja
Interdisciplinarne prirodne znanosti, Farmacija, Nutricionizam

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