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 - Funding Information:
This work was partly supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia, as a part of the Projects No. 172041 and No. 175035. One of the authors (B.T.) is thankful to the Ministry of Science and Technology of the Republic of Srpska for funding the study through the Project 19/6-020/961-169/14.
Funding Information:
This work was partly supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia, as a part of the Projects No. 172041 and No. 175035. One of the authors (B.T.) is thankful to the Ministry of Science and Technology of the Republic of Srpska for funding the study through the Project 19/6- 020/961-169/14.
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 -