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Synthesis and Biocompatibility Studies of New Iminodiacetic Acid Derivatives.

ABSTRACT: 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.

SUBMITTER: Markowicz-Piasecka M

PROVIDER: S-EPMC6149924 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Biocompatibility Studies of Gadolinium Complexes with Iminodiacetic Acid Derivatives.

Project description:Apart from using as radiopharmaceuticals, iminodiacetic acid derivatives, after complexation with gadolinium, have been also tested as MRI CAs (magnetic resonance imaging contrast agents) since they show high affinity to hepatocytes and therefore provide high-resolution MRI of the liver. The purpose of this study was to evaluate the biocompatibility of four gadolinium complexes with iminodiacetic acid (IDA) derivatives differing in substituent in aromatic ring by estimating their influence on plasma hemostasis, integrity of erythrocyte membrane, and toxicity towards human umbilical vein endothelial cells (HUVECs). The influence of gadolinium-based CAs on plasma hemostasis was evaluated by measuring PT (prothrombin time), APTT (activated partial tromboplastin time), and TT (thrombin time). The effects of tested compounds on RBCs (Red Blood Cells) were assessed using hemolysis assay and microscopy studies. The influence of gadolinium complexes on the barrier properties of HUVECs was assessed by means of real-time method based on the measurements of the impedance changes of the cells. Gadolinium complexes did not affect significantly PT and TT. APTT measurements revealed significant prolongation in the presence of all tested gadolinium complexes at the concentration higher than 0.5 ?mol/mL. Hemolysis assay showed that compounds with alkyl substituents in benzene ring without halogen atom (1-3) do not exert unfavorable effect on the integrity of erythrocyte membrane over the entire concentration range. All gadolinium complexes at 1.0 ?mol/mL contribute to the decrease in HUVEC viability and integrity. To conclude, the study describes biocompatibility studies of gadolinium-based CAs, provides additional insight into their potential toxicity associated with systemic administration, and underscores the necessity for further research.

| S-EPMC6469645 | biostudies-literature

Design, synthesis, molecular modeling and DNA-binding studies of new barbituric acid derivatives

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| S-EPMC4077457 | biostudies-literature

New Estrone Oxime Derivatives: Synthesis, Cytotoxic Evaluation and Docking Studies.

Project description:The interest in the introduction of the oxime group in molecules aiming to improve their biological effects is increasing. This work aimed to develop new steroidal oximes of the estrane series with potential antitumor interest. For this, several oximes were synthesized by reaction of hydroxylamine with the 17-ketone of estrone derivatives. Then, their cytotoxicity was evaluated in six cell lines. An estrogenicity assay, a cell cycle distribution analysis and a fluorescence microscopy study with Hoechst 3358 staining were performed with the most promising compound. In addition, molecular docking studies against estrogen receptor α, steroid sulfatase, 17β-hydroxysteroid dehydrogenase type 1 and β-tubulin were also accomplished. The 2-nitroestrone oxime showed higher cytotoxicity than the parent compound on MCF-7 cancer cells. Furthermore, the oximes bearing halogen groups in A-ring evidenced selectivity for HepaRG cells. Remarkably, the Δ9,11-estrone oxime was the most cytotoxic and arrested LNCaP cells in the G2/M phase. Fluorescence microscopy studies showed the presence of condensed DNA typical of prophase and condensed and fragmented nuclei characteristic of apoptosis. However, this oxime promoted the proliferation of T47-D cells. Interestingly, molecular docking studies estimated a strong interaction between Δ9,11-estrone oxime and estrogen receptor α and β-tubulin, which may account for the described effects.

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Synthesis of Pyrazole-Thiobarbituric Acid Derivatives: Antimicrobial Activity and Docking Studies.

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Synthesis and dynamics studies of barbituric acid derivatives as urease inhibitors.

Project description:BackgroundDiscovery of potent inhibitors of urease (jack bean) enzyme is the first step in the development of drugs against diseases caused by ureolytic enzyme.ResultsThirty-two derivatives of barbituric acid as zwitterionic adducts of diethyl ammonium salts were synthesized. All synthesized compounds (4a-z and 5a-s) were screened for their in vitro inhibition potential against urease enzyme (jack bean urease). The compounds 4i (IC50 = 17.6 ± 0.23 µM) and 5l (IC50 = 17.2 ± 0.44 µM) were found to be the most active members of the series, and showed several fold more urease inhibition activity than the standard compound thiourea (IC50 = 21.2 ± 1.3 µM). Whereas, compounds 4a-b, 4d-e, 4g-h, 4j-4r, 4x, 4z, 5b, 5e, 5k, 5n-5q having IC50 values in the range of 22.7 ± 0.20 µM-43.8 ± 0.33 µM, were also found as potent urease inhibitors. Furthermore, Molecular Dynamics simulation and molecular docking studies were carried out to analyze the binding mode of barbituric acid derivatives using MOE. During MD simulation enol form is found to be more stable over its keto form due to their coordination with catalytic Nickel ion of Urease. Additionally, structural-activity relationship using automated docking method was applied where the compounds with high biological activity are deeply buried within the binding pocket of urease. As multiple hydrophilic crucial interactions with Ala169, KCX219, Asp362 and Ala366 stabilize the compound within the binding site, thus contributing greater activity.ConclusionsThis research study is useful for the discovery of economically, efficient viable new drug against infectious diseases.Graphical abstract:STD. Thiourea (IC50 = 21.2 ± 1.3 µM).

| S-EPMC4648982 | biostudies-literature

Synthesis, Biological Activity and Molecular Docking Studies of Novel Nicotinic Acid Derivatives.

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| S-EPMC8911400 | biostudies-literature

Evaluation of poly(amidoamine) dendrimers as potential carriers of iminodiacetic derivatives using solubility studies and 2D-NOESY NMR spectroscopy.

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| S-EPMC3473130 | biostudies-literature

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