Synthesis and Biocompatibility Studies of New Iminodiacetic Acid Derivatives

Background: Iminodiacetic acid (IDA) derivatives can be used as ligands to form complexes with technetium, with potential application as hepatobiliary diagnostic agents. The aim of this study was to synthesize five novel IDA derivatives and to compare their effects on plasma haemostasis with clinica...

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Main Authors: Magdalena Markowicz-Piasecka, Piotr Dębski, Elżbieta Mikiciuk-Olasik, Joanna Sikora
Format: Article
Language:English
Published: MDPI AG 2017-12-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/22/12/2265
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author Magdalena Markowicz-Piasecka
Piotr Dębski
Elżbieta Mikiciuk-Olasik
Joanna Sikora
author_facet Magdalena Markowicz-Piasecka
Piotr Dębski
Elżbieta Mikiciuk-Olasik
Joanna Sikora
author_sort Magdalena Markowicz-Piasecka
collection DOAJ
description Background: Iminodiacetic acid (IDA) derivatives can be used as ligands to form complexes with technetium, with potential application as hepatobiliary diagnostic agents. The aim of this study was to synthesize five novel IDA derivatives and to compare their effects on plasma haemostasis with clinically approved ligands for technetium complexation. Methods: The influence of synthesized IDA derivatives on plasma haemostasis was evaluated spectrophotometrically by clot formation and lysis test (CL-test), coagulation assay, Prothrombin Time and Activated Partial Tromboplastin Time. The effects of the tested compounds on erythrocytes were assessed using haemolysis assays, microscopy and flow cytometry studies. Results: Despite their significant influence on the kinetic parameters of the process of clot formation and fibrinolysis, the tested ligands, at potential diagnostic concentrations, did not alter the overall potential of clot formation and lysis (CLAUC). At potential diagnostic concentrations (0.4 μmol/mL) all the tested compounds showed no adverse effects on the membranes of RBCs (Red Blood Cells). Conclusion: IDA derivatives with methoxy substituents in aromatic ring, exert multidirectional effects on plasma haemostasis and should be considered safe as their significant impacts were mostly observed at 4 μmol/mL, which is about 10-fold higher than the theoretical plasma concentrations of these compounds.
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spelling doaj.art-f97fe134c8784a4580e552a94e99b9d12022-12-21T18:51:12ZengMDPI AGMolecules1420-30492017-12-012212226510.3390/molecules22122265molecules22122265Synthesis and Biocompatibility Studies of New Iminodiacetic Acid DerivativesMagdalena Markowicz-Piasecka0Piotr Dębski1Elżbieta Mikiciuk-Olasik2Joanna Sikora3Laboratory of Bioanalysis, Department of Pharmaceutical Chemistry, Drug Analysis and Radiopharmacy, Medical University of Lodz, ul. Muszyńskiego1, 90-151 Lodz, PolandStudents Research Group, Laboratory of Bioanalysis, Department of Pharmaceutical Chemistry, Drug Analysis and Radiopharmacy, Medical University of Lodz, ul. Muszyńskiego 1, 90-151 Lodz, PolandDepartment of Pharmaceutical Chemistry, Drug Analysis and Radiopharmacy, Medical University of Lodz, ul. Muszyńskiego 1, 90-151 Lodz, PolandLaboratory of Bioanalysis, Department of Pharmaceutical Chemistry, Drug Analysis and Radiopharmacy, Medical University of Lodz, ul. Muszyńskiego1, 90-151 Lodz, PolandBackground: Iminodiacetic acid (IDA) derivatives can be used as ligands to form complexes with technetium, with potential application as hepatobiliary diagnostic agents. The aim of this study was to synthesize five novel IDA derivatives and to compare their effects on plasma haemostasis with clinically approved ligands for technetium complexation. Methods: The influence of synthesized IDA derivatives on plasma haemostasis was evaluated spectrophotometrically by clot formation and lysis test (CL-test), coagulation assay, Prothrombin Time and Activated Partial Tromboplastin Time. The effects of the tested compounds on erythrocytes were assessed using haemolysis assays, microscopy and flow cytometry studies. Results: Despite their significant influence on the kinetic parameters of the process of clot formation and fibrinolysis, the tested ligands, at potential diagnostic concentrations, did not alter the overall potential of clot formation and lysis (CLAUC). At potential diagnostic concentrations (0.4 μmol/mL) all the tested compounds showed no adverse effects on the membranes of RBCs (Red Blood Cells). Conclusion: IDA derivatives with methoxy substituents in aromatic ring, exert multidirectional effects on plasma haemostasis and should be considered safe as their significant impacts were mostly observed at 4 μmol/mL, which is about 10-fold higher than the theoretical plasma concentrations of these compounds.https://www.mdpi.com/1420-3049/22/12/2265iminodiacetic acidradiopharmaceuticalsbiocompatibilityhaemostasis
spellingShingle Magdalena Markowicz-Piasecka
Piotr Dębski
Elżbieta Mikiciuk-Olasik
Joanna Sikora
Synthesis and Biocompatibility Studies of New Iminodiacetic Acid Derivatives
Molecules
iminodiacetic acid
radiopharmaceuticals
biocompatibility
haemostasis
title Synthesis and Biocompatibility Studies of New Iminodiacetic Acid Derivatives
title_full Synthesis and Biocompatibility Studies of New Iminodiacetic Acid Derivatives
title_fullStr Synthesis and Biocompatibility Studies of New Iminodiacetic Acid Derivatives
title_full_unstemmed Synthesis and Biocompatibility Studies of New Iminodiacetic Acid Derivatives
title_short Synthesis and Biocompatibility Studies of New Iminodiacetic Acid Derivatives
title_sort synthesis and biocompatibility studies of new iminodiacetic acid derivatives
topic iminodiacetic acid
radiopharmaceuticals
biocompatibility
haemostasis
url https://www.mdpi.com/1420-3049/22/12/2265
work_keys_str_mv AT magdalenamarkowiczpiasecka synthesisandbiocompatibilitystudiesofnewiminodiaceticacidderivatives
AT piotrdebski synthesisandbiocompatibilitystudiesofnewiminodiaceticacidderivatives
AT elzbietamikiciukolasik synthesisandbiocompatibilitystudiesofnewiminodiaceticacidderivatives
AT joannasikora synthesisandbiocompatibilitystudiesofnewiminodiaceticacidderivatives