Prediction of in vivo Bioavailibility by in vitro Characterization of Ethylenediamine Dipropanoic Acid Derivatives with Cytotoxic Activity
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O,O'-diethyl-(S, S)-ethylenediamine-N, N'-di-2-(3-cyclohexyl) propanoate (DE-EDCP) is novel substance with cytotoxic activity in human leukemic cells. The aim of this study has been to predict in vivo bioavailability of the DE-EDCP and its potential metabolite (S, S)-ethylenediamine-N, N'-di-2-(3-cyclohexyl) propanoic acid (EDCP) by in vitro characterization which includes determination of lipophilicity and passive membrane permeability. There has also been evaluated inter-laboratory reproducibility of the bio-analytical method which was previously developed and validated for non-clinical study of the DE-EDCP and EDCP. Distribution coefficient n-octanol/water was 1.68 and 0.03, and apparent permeability coefficient was 4 x 10(-4) cm/s and 20 x 10(-4) cm/s, for the DE-EDCP and EDCP, respectively. Observed results have shown that the DE-EDCP is more lipophilic with better membrane retention, but the EDCP has better pass through the membrane. Also, there has been demonstrated a reproducib...ility and robustness of the proposed bio-analytical method.
Keywords:Transfer of the UHPLC-MS/MS / cross validation / (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl) propanoic acid esters / membrane permeability / lipophilicity
Source:Acta Chimica Slovenica, 2018, 65, 1, 59-64
- Slovensko Kemijsko Drustvo, Ljubljana