Prediction of in vivo bioavailibility by in vitro characterization of ethylenediamine dipropanoic acid derivatives with cytotoxic activity

Biljana K. Tubic*, Sandra S. Vladimirov, Bojan D. Marković, Tibor J. Sabo

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)59-64
Number of pages6
JournalActa Chimica Slovenica
Volume65
Issue number1
DOIs
Publication statusPublished - 2018
Externally publishedYes

Keywords

  • (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl) propanoic acid esters
  • Cross validation
  • Lipophilicity
  • Membrane permeability
  • Transfer of the UHPLC-MS/MS

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