A biological, fluorescence and computational examination of synthetic coumarin derivatives with antithrombotic potential
Copyright © 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved..
BACKGROUND: Scientists still look for new drugs, which have anticoagulant properties. This is so important because existing anticoagulant drugs give many side effects, for example major bleeding. In this study we examined nine coumarin derivatives - candidates to be future antithrombotic drugs, which were synthetized and crystallized in our previous paper.
METHODS: Here we show the fluorescence and fluorescence quenching of coumarin derivatives with di- or trimethoxybenzylamine moieties in C-3 position. All nine compounds were checked by lactate dehydrogenase assay to examine their cytotoxic activity on hepatic cells. We also investigated the other biological properties (bioactivity, drug-likeness and blind docking) using computational tools. Lipophilicity coefficient logP of all obtained compounds was determined using by RP-TLC and compared to theoretical predictions.
RESULTS: The obtained coumarins exhibited low lipophilic character. The substances bound with HSA and did not demonstrate cytotoxicity against isolated liver cells. The most interesting compound (3b) possessed two methoxy- group in 2- and 4-position in benzene ring, ability to interact with two HSA binding sites and probably smaller steric hindrance in comparison to other synthesized derivatives.
CONCLUSIONS: Our present study shows that after examination of fluorescence, cytotoxic activity, lipophilicity, theoretical bioactivity, drug-likeness and blind docking of our synthesized compounds they have potential as antithrombotic medicines and may be candidates to be drugs after further studies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:70 |
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| Enthalten in: |
Pharmacological reports : PR - 70(2018), 6 vom: 15. Dez., Seite 1057-1064 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kasperkiewicz, Kinga [VerfasserIn] |
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| Links: |
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| Themen: |
A4VZ22K1WT |
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| Anmerkungen: |
Date Completed 14.01.2019 Date Revised 06.01.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.pharep.2018.06.002 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM289320542 |
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| 100 | 1 | |a Kasperkiewicz, Kinga |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A biological, fluorescence and computational examination of synthetic coumarin derivatives with antithrombotic potential |
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| 500 | |a Date Completed 14.01.2019 | ||
| 500 | |a Date Revised 06.01.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a BACKGROUND: Scientists still look for new drugs, which have anticoagulant properties. This is so important because existing anticoagulant drugs give many side effects, for example major bleeding. In this study we examined nine coumarin derivatives - candidates to be future antithrombotic drugs, which were synthetized and crystallized in our previous paper | ||
| 520 | |a METHODS: Here we show the fluorescence and fluorescence quenching of coumarin derivatives with di- or trimethoxybenzylamine moieties in C-3 position. All nine compounds were checked by lactate dehydrogenase assay to examine their cytotoxic activity on hepatic cells. We also investigated the other biological properties (bioactivity, drug-likeness and blind docking) using computational tools. Lipophilicity coefficient logP of all obtained compounds was determined using by RP-TLC and compared to theoretical predictions | ||
| 520 | |a RESULTS: The obtained coumarins exhibited low lipophilic character. The substances bound with HSA and did not demonstrate cytotoxicity against isolated liver cells. The most interesting compound (3b) possessed two methoxy- group in 2- and 4-position in benzene ring, ability to interact with two HSA binding sites and probably smaller steric hindrance in comparison to other synthesized derivatives | ||
| 520 | |a CONCLUSIONS: Our present study shows that after examination of fluorescence, cytotoxic activity, lipophilicity, theoretical bioactivity, drug-likeness and blind docking of our synthesized compounds they have potential as antithrombotic medicines and may be candidates to be drugs after further studies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cell viability | |
| 650 | 4 | |a Coumarin derivatives | |
| 650 | 4 | |a Fluorescence quenching | |
| 650 | 4 | |a Hepatocytes | |
| 650 | 4 | |a LDH assay | |
| 650 | 7 | |a Coumarins |2 NLM | |
| 650 | 7 | |a Fibrinolytic Agents |2 NLM | |
| 650 | 7 | |a coumarin |2 NLM | |
| 650 | 7 | |a A4VZ22K1WT |2 NLM | |
| 700 | 1 | |a Ponczek, Michal B |e verfasserin |4 aut | |
| 700 | 1 | |a Budzisz, Elzbieta |e verfasserin |4 aut | |
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