Investigation of metabolic properties and effects of 17β-carboxamide glucocorticoids on human peripheral blood leukocytes
© 2018 Deutsche Pharmazeutische Gesellschaft..
The biological activity of three previously synthesized 17β-carboxamide glucocorticoids (BG, BEG, and MPEA) was tested in vitro on mitogen stimulated and non-stimulated peripheral blood mononuclear cells (MNCs) and granulocytes from human healthy donors, and the results were compared to the conventional glucocorticoid dexamethasone. The tested 17β-carboxamide glucocorticoids did not induce decreases in MNC viability and proliferation, while modulation of reactive oxygen species (ROS) synthesis in granulocytes was dependent on the cell donor. The obtained results indicate the possibility of avoidance of strong lymphocyte suppression, which is generally recognized during administration of conventional glucocorticoids. Furthermore, the metabolism of the tested derivatives was predicted in silico. The predicted metabolites were synthesized and the in silico results were confirmed by in vitro evaluation of the metabolism of BG, BEG, and MPEA in human serum and in cultures of peripheral blood MNCs. The results of the biological activity and metabolism evaluation and of previous in vivo evaluations of biological activity indicate the soft drug nature of BG, BEG, and MPEA. In order to be fully considered as soft glucocorticoids, further investigations on the toxicity and activity of the formed metabolites are required.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:351 |
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| Enthalten in: |
Archiv der Pharmazie - 351(2018), 5 vom: 01. Mai, Seite e1700371 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dobričić, Vladimir [VerfasserIn] |
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| Links: |
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| Themen: |
7S5I7G3JQL |
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| Anmerkungen: |
Date Completed 20.09.2018 Date Revised 20.09.2018 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/ardp.201700371 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM283091886 |
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| 100 | 1 | |a Dobričić, Vladimir |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Investigation of metabolic properties and effects of 17β-carboxamide glucocorticoids on human peripheral blood leukocytes |
| 264 | 1 | |c 2018 | |
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| 500 | |a Date Completed 20.09.2018 | ||
| 500 | |a Date Revised 20.09.2018 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2018 Deutsche Pharmazeutische Gesellschaft. | ||
| 520 | |a The biological activity of three previously synthesized 17β-carboxamide glucocorticoids (BG, BEG, and MPEA) was tested in vitro on mitogen stimulated and non-stimulated peripheral blood mononuclear cells (MNCs) and granulocytes from human healthy donors, and the results were compared to the conventional glucocorticoid dexamethasone. The tested 17β-carboxamide glucocorticoids did not induce decreases in MNC viability and proliferation, while modulation of reactive oxygen species (ROS) synthesis in granulocytes was dependent on the cell donor. The obtained results indicate the possibility of avoidance of strong lymphocyte suppression, which is generally recognized during administration of conventional glucocorticoids. Furthermore, the metabolism of the tested derivatives was predicted in silico. The predicted metabolites were synthesized and the in silico results were confirmed by in vitro evaluation of the metabolism of BG, BEG, and MPEA in human serum and in cultures of peripheral blood MNCs. The results of the biological activity and metabolism evaluation and of previous in vivo evaluations of biological activity indicate the soft drug nature of BG, BEG, and MPEA. In order to be fully considered as soft glucocorticoids, further investigations on the toxicity and activity of the formed metabolites are required | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a anti-inflammatory activity | |
| 650 | 4 | |a granulocytes | |
| 650 | 4 | |a metabolism | |
| 650 | 4 | |a peripheral blood mononuclear cells | |
| 650 | 7 | |a Glucocorticoids |2 NLM | |
| 650 | 7 | |a Reactive Oxygen Species |2 NLM | |
| 650 | 7 | |a Dexamethasone |2 NLM | |
| 650 | 7 | |a 7S5I7G3JQL |2 NLM | |
| 700 | 1 | |a Drvenica, Ivana |e verfasserin |4 aut | |
| 700 | 1 | |a Stančić, Ana |e verfasserin |4 aut | |
| 700 | 1 | |a Mihailović, Marija |e verfasserin |4 aut | |
| 700 | 1 | |a Čudina, Olivera |e verfasserin |4 aut | |
| 700 | 1 | |a Bugarski, Diana |e verfasserin |4 aut | |
| 700 | 1 | |a Ilić, Vesna |e verfasserin |4 aut | |
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