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17 beta-carboxamide steroids - in vitro prediction of human skin permeability and retention using PAMPA technique

Authorized Users Only
2014
Authors
Dobričić, Vladimir
Marković, Bojan
Nikolić, Katarina
Savić, Vladimir
Vladimirov, Sote
Čudina, Olivera
Article (Published version)
Metadata
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Abstract
In this paper, twenty-two 17 beta-carboxamide steroids were synthesized from five corticosteroids (hydrocortisone, prednisolone, methylprednisolone, dexamethasone and betamethasone) in two steps. The first step was periodic acid oxydation of these corticosteroids to corresponding cortienic acids and the second step was amidation of thus obtained cortienic acids with esterified L-amino acids. These compounds are potential soft corticosteroids with local anti-inflammatory activity in the skin. Parallel artificial membrane permeability assay (PAMPA) was applied in order to predict permeability and retention of these compounds in human skin. Comparison of permeability and retention parameters between 17 beta-carboxamide steroids and corresponding corticosteroids was performed. Compounds with significantly higher retention were identified and the derivative that does not have significantly higher permeability was underlined. Molecular structures of all compounds were optimized by use of Gau...ssian semiempirical/PM3 method. Geometrical, thermodynamic, physicochemical and electronical molecular parameters of the optimized structures were calculated and quantitative structure-property relationship (QSPR) analysis was performed in order to explain permeability and retention of these compounds. ANN-, PLS- and MLR-QSPR models were created. Quality of these models was evaluated by commonly used statistical parameters and the most reliable models were selected. Analyzing descriptors in the selected models, main molecular properties that influence permeability and retention in the PAMPA artificial membrane were identified. Based on these data, further structural modifications could be applied in order to increase retention without significant increase of permeability, which can positively affect potential local antiinflammatory activity of these compounds. Selected QSPR models could be used as in silico tool for predicting human skin permeability and retention of novel 17 beta-carboxamide steroids without performing PAMPA experiments.

Keywords:
Soft corticosteroids / PAMPA / Human skin permeability and retention / Quantitative structure property relationship
Source:
European Journal of Pharmaceutical Sciences, 2014, 52, 95-108
Publisher:
  • Elsevier Science BV, Amsterdam
Funding / projects:
  • Development of molecules with antiinflammatory and cardioprotective activity: structural modifications, modelling, physicochemical characterization and formulation investigations (RS-172041)

DOI: 10.1016/j.ejps.2013.10.017

ISSN: 0928-0987

PubMed: 24239478

WoS: 000331022100012

Scopus: 2-s2.0-84888236652
[ Google Scholar ]
29
24
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/2175
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Dobričić, Vladimir
AU  - Marković, Bojan
AU  - Nikolić, Katarina
AU  - Savić, Vladimir
AU  - Vladimirov, Sote
AU  - Čudina, Olivera
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2175
AB  - In this paper, twenty-two 17 beta-carboxamide steroids were synthesized from five corticosteroids (hydrocortisone, prednisolone, methylprednisolone, dexamethasone and betamethasone) in two steps. The first step was periodic acid oxydation of these corticosteroids to corresponding cortienic acids and the second step was amidation of thus obtained cortienic acids with esterified L-amino acids. These compounds are potential soft corticosteroids with local anti-inflammatory activity in the skin. Parallel artificial membrane permeability assay (PAMPA) was applied in order to predict permeability and retention of these compounds in human skin. Comparison of permeability and retention parameters between 17 beta-carboxamide steroids and corresponding corticosteroids was performed. Compounds with significantly higher retention were identified and the derivative that does not have significantly higher permeability was underlined. Molecular structures of all compounds were optimized by use of Gaussian semiempirical/PM3 method. Geometrical, thermodynamic, physicochemical and electronical molecular parameters of the optimized structures were calculated and quantitative structure-property relationship (QSPR) analysis was performed in order to explain permeability and retention of these compounds. ANN-, PLS- and MLR-QSPR models were created. Quality of these models was evaluated by commonly used statistical parameters and the most reliable models were selected. Analyzing descriptors in the selected models, main molecular properties that influence permeability and retention in the PAMPA artificial membrane were identified. Based on these data, further structural modifications could be applied in order to increase retention without significant increase of permeability, which can positively affect potential local antiinflammatory activity of these compounds. Selected QSPR models could be used as in silico tool for predicting human skin permeability and retention of novel 17 beta-carboxamide steroids without performing PAMPA experiments.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmaceutical Sciences
T1  - 17 beta-carboxamide steroids - in vitro prediction of human skin permeability and retention using PAMPA technique
VL  - 52
SP  - 95
EP  - 108
DO  - 10.1016/j.ejps.2013.10.017
UR  - conv_3022
ER  - 
@article{
author = "Dobričić, Vladimir and Marković, Bojan and Nikolić, Katarina and Savić, Vladimir and Vladimirov, Sote and Čudina, Olivera",
year = "2014",
abstract = "In this paper, twenty-two 17 beta-carboxamide steroids were synthesized from five corticosteroids (hydrocortisone, prednisolone, methylprednisolone, dexamethasone and betamethasone) in two steps. The first step was periodic acid oxydation of these corticosteroids to corresponding cortienic acids and the second step was amidation of thus obtained cortienic acids with esterified L-amino acids. These compounds are potential soft corticosteroids with local anti-inflammatory activity in the skin. Parallel artificial membrane permeability assay (PAMPA) was applied in order to predict permeability and retention of these compounds in human skin. Comparison of permeability and retention parameters between 17 beta-carboxamide steroids and corresponding corticosteroids was performed. Compounds with significantly higher retention were identified and the derivative that does not have significantly higher permeability was underlined. Molecular structures of all compounds were optimized by use of Gaussian semiempirical/PM3 method. Geometrical, thermodynamic, physicochemical and electronical molecular parameters of the optimized structures were calculated and quantitative structure-property relationship (QSPR) analysis was performed in order to explain permeability and retention of these compounds. ANN-, PLS- and MLR-QSPR models were created. Quality of these models was evaluated by commonly used statistical parameters and the most reliable models were selected. Analyzing descriptors in the selected models, main molecular properties that influence permeability and retention in the PAMPA artificial membrane were identified. Based on these data, further structural modifications could be applied in order to increase retention without significant increase of permeability, which can positively affect potential local antiinflammatory activity of these compounds. Selected QSPR models could be used as in silico tool for predicting human skin permeability and retention of novel 17 beta-carboxamide steroids without performing PAMPA experiments.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmaceutical Sciences",
title = "17 beta-carboxamide steroids - in vitro prediction of human skin permeability and retention using PAMPA technique",
volume = "52",
pages = "95-108",
doi = "10.1016/j.ejps.2013.10.017",
url = "conv_3022"
}
Dobričić, V., Marković, B., Nikolić, K., Savić, V., Vladimirov, S.,& Čudina, O.. (2014). 17 beta-carboxamide steroids - in vitro prediction of human skin permeability and retention using PAMPA technique. in European Journal of Pharmaceutical Sciences
Elsevier Science BV, Amsterdam., 52, 95-108.
https://doi.org/10.1016/j.ejps.2013.10.017
conv_3022
Dobričić V, Marković B, Nikolić K, Savić V, Vladimirov S, Čudina O. 17 beta-carboxamide steroids - in vitro prediction of human skin permeability and retention using PAMPA technique. in European Journal of Pharmaceutical Sciences. 2014;52:95-108.
doi:10.1016/j.ejps.2013.10.017
conv_3022 .
Dobričić, Vladimir, Marković, Bojan, Nikolić, Katarina, Savić, Vladimir, Vladimirov, Sote, Čudina, Olivera, "17 beta-carboxamide steroids - in vitro prediction of human skin permeability and retention using PAMPA technique" in European Journal of Pharmaceutical Sciences, 52 (2014):95-108,
https://doi.org/10.1016/j.ejps.2013.10.017 .,
conv_3022 .

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