TY - JOUR
T1 - Prediction of in vivo bioavailibility by in vitro characterization of ethylenediamine dipropanoic acid derivatives with cytotoxic activity
AU - Tubic, Biljana K.
AU - Vladimirov, Sandra S.
AU - Marković, Bojan D.
AU - Sabo, Tibor J.
N1 - Publisher Copyright:
©2018 Slovensko Kemijsko Drustvo. All Rights Reserved.
PY - 2018
Y1 - 2018
N2 - 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 × 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 reproducibility and robustness of the proposed bio-analytical method.
AB - 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 × 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 reproducibility and robustness of the proposed bio-analytical method.
KW - (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl) propanoic acid esters
KW - Cross validation
KW - Lipophilicity
KW - Membrane permeability
KW - Transfer of the UHPLC-MS/MS
UR - http://www.scopus.com/inward/record.url?scp=85044361213&partnerID=8YFLogxK
U2 - 10.17344/acsi.2017.3477
DO - 10.17344/acsi.2017.3477
M3 - Article
C2 - 29562114
AN - SCOPUS:85044361213
SN - 1318-0207
VL - 65
SP - 59
EP - 64
JO - Acta Chimica Slovenica
JF - Acta Chimica Slovenica
IS - 1
ER -