Investigation of metabolic properties and effects of 17 beta-carboxamide glucocorticoids on human peripheral blood leukocytes
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2018
Authors
Dobričić, Vladimir
Drvenica, Ivana

Stancić, Ana

Mihailović, Marija
Čudina, Olivera

Bugarski, Diana
Ilić, Vesna

Article (Published version)

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The biological activity of three previously synthesized 17 beta-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 17 beta-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 periphe...ral 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.
Keywords:
anti-inflammatory activity / metabolism / peripheral blood mononuclear cells / granulocytesSource:
Archiv der Pharmazie, 2018, 351, 5Publisher:
- Wiley-VCH Verlag GMBH, Weinheim
Funding / projects:
DOI: 10.1002/ardp.201700371
ISSN: 0365-6233
PubMed: 29660818
WoS: 000431489000004
Scopus: 2-s2.0-85045727394
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PharmacyTY - JOUR AU - Dobričić, Vladimir AU - Drvenica, Ivana AU - Stancić, Ana AU - Mihailović, Marija AU - Čudina, Olivera AU - Bugarski, Diana AU - Ilić, Vesna PY - 2018 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3162 AB - The biological activity of three previously synthesized 17 beta-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 17 beta-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. PB - Wiley-VCH Verlag GMBH, Weinheim T2 - Archiv der Pharmazie T1 - Investigation of metabolic properties and effects of 17 beta-carboxamide glucocorticoids on human peripheral blood leukocytes VL - 351 IS - 5 DO - 10.1002/ardp.201700371 ER -
@article{ author = "Dobričić, Vladimir and Drvenica, Ivana and Stancić, Ana and Mihailović, Marija and Čudina, Olivera and Bugarski, Diana and Ilić, Vesna", year = "2018", abstract = "The biological activity of three previously synthesized 17 beta-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 17 beta-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.", publisher = "Wiley-VCH Verlag GMBH, Weinheim", journal = "Archiv der Pharmazie", title = "Investigation of metabolic properties and effects of 17 beta-carboxamide glucocorticoids on human peripheral blood leukocytes", volume = "351", number = "5", doi = "10.1002/ardp.201700371" }
Dobričić, V., Drvenica, I., Stancić, A., Mihailović, M., Čudina, O., Bugarski, D.,& Ilić, V.. (2018). Investigation of metabolic properties and effects of 17 beta-carboxamide glucocorticoids on human peripheral blood leukocytes. in Archiv der Pharmazie Wiley-VCH Verlag GMBH, Weinheim., 351(5). https://doi.org/10.1002/ardp.201700371
Dobričić V, Drvenica I, Stancić A, Mihailović M, Čudina O, Bugarski D, Ilić V. Investigation of metabolic properties and effects of 17 beta-carboxamide glucocorticoids on human peripheral blood leukocytes. in Archiv der Pharmazie. 2018;351(5). doi:10.1002/ardp.201700371 .
Dobričić, Vladimir, Drvenica, Ivana, Stancić, Ana, Mihailović, Marija, Čudina, Olivera, Bugarski, Diana, Ilić, Vesna, "Investigation of metabolic properties and effects of 17 beta-carboxamide glucocorticoids on human peripheral blood leukocytes" in Archiv der Pharmazie, 351, no. 5 (2018), https://doi.org/10.1002/ardp.201700371 . .