In silico–in vitro estimation of lipophilicity and permeability association for succinimide derivatives using chromatographic anisotropic systems and parallel artificial membrane permeability assay
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2022
Authors
Vidović, DunjaMilošević, Nataša
Pavlović, Nebojša
Todorović, Nemanja
Panić Čanji, Jelena
Ćurčić, Jelena
Banjac, Nebojša
Trišović, Nemanja
Božić, Bojan
Lalić-Popović, Mladena
Article (Published version)
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Passive permeability is one of the key features that determine absorbability and one of the most studied properties in the early phases of drug development. Newly synthesized succinimide derivatives from two different series (1-aryl-3-methylsuccinimides and 1-aryl-3-ethyl-3-methylsuccinimides) with high biological potential have been subjected to estimation of their passive permeability and their association with (a) experimentally obtained anisotropic lipophilicity, (b) in silico–calculated lipophilicity and (c) in silico–predicted permeability and absorbability. Non-cellular-based parallel artificial membrane permeability assay was applied for quantifying their passive permeation, expressed as logPapp. Passive permeation was governed by the lipophilicity of the analysed compounds, and anisotropic lipophilicity was related with statistically significant passive transcellular diffusion (r2 = 0.614, P < 0.001). Moreover, experimentally determined passive permeability, logPapp, was stati...stically significantly associated with both in silico–predicted absorption constant, ka (r2 = 0.7886, P < 0.001), and human intestinal absorption (HIA) in percentage (r2 = 0.484, P < 0.001), respectively. However, there was no statistically significant relationship between experimentally obtained permeability on non-cellular-based model and in silico–predicted Caco-2 permeability based on the predictions conducted on two different software. Based on the obtained results, anisotropic systems are promising surrogates for determining lipophilicity, except for compounds with acidic functional groups that are completely ionized under (pH = 7.4).
Keywords:
chromatography / in silico / lipophilicity / parallel artificial membrane permeability assaySource:
Biomedical Chromatography, 2022Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200114 (University of Novi Sad, Faculty of Medicine) (RS-MESTD-inst-2020-200114)
DOI: 10.1002/bmc.5413
ISSN: 0269-3879
WoS: 00080498990000
Scopus: 2-s2.0-85131157068
Institution/Community
Tehnološko-metalurški fakultetTY - JOUR AU - Vidović, Dunja AU - Milošević, Nataša AU - Pavlović, Nebojša AU - Todorović, Nemanja AU - Panić Čanji, Jelena AU - Ćurčić, Jelena AU - Banjac, Nebojša AU - Trišović, Nemanja AU - Božić, Bojan AU - Lalić-Popović, Mladena PY - 2022 UR - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/5150 AB - Passive permeability is one of the key features that determine absorbability and one of the most studied properties in the early phases of drug development. Newly synthesized succinimide derivatives from two different series (1-aryl-3-methylsuccinimides and 1-aryl-3-ethyl-3-methylsuccinimides) with high biological potential have been subjected to estimation of their passive permeability and their association with (a) experimentally obtained anisotropic lipophilicity, (b) in silico–calculated lipophilicity and (c) in silico–predicted permeability and absorbability. Non-cellular-based parallel artificial membrane permeability assay was applied for quantifying their passive permeation, expressed as logPapp. Passive permeation was governed by the lipophilicity of the analysed compounds, and anisotropic lipophilicity was related with statistically significant passive transcellular diffusion (r2 = 0.614, P < 0.001). Moreover, experimentally determined passive permeability, logPapp, was statistically significantly associated with both in silico–predicted absorption constant, ka (r2 = 0.7886, P < 0.001), and human intestinal absorption (HIA) in percentage (r2 = 0.484, P < 0.001), respectively. However, there was no statistically significant relationship between experimentally obtained permeability on non-cellular-based model and in silico–predicted Caco-2 permeability based on the predictions conducted on two different software. Based on the obtained results, anisotropic systems are promising surrogates for determining lipophilicity, except for compounds with acidic functional groups that are completely ionized under (pH = 7.4). T2 - Biomedical Chromatography T1 - In silico–in vitro estimation of lipophilicity and permeability association for succinimide derivatives using chromatographic anisotropic systems and parallel artificial membrane permeability assay DO - 10.1002/bmc.5413 ER -
@article{ author = "Vidović, Dunja and Milošević, Nataša and Pavlović, Nebojša and Todorović, Nemanja and Panić Čanji, Jelena and Ćurčić, Jelena and Banjac, Nebojša and Trišović, Nemanja and Božić, Bojan and Lalić-Popović, Mladena", year = "2022", abstract = "Passive permeability is one of the key features that determine absorbability and one of the most studied properties in the early phases of drug development. Newly synthesized succinimide derivatives from two different series (1-aryl-3-methylsuccinimides and 1-aryl-3-ethyl-3-methylsuccinimides) with high biological potential have been subjected to estimation of their passive permeability and their association with (a) experimentally obtained anisotropic lipophilicity, (b) in silico–calculated lipophilicity and (c) in silico–predicted permeability and absorbability. Non-cellular-based parallel artificial membrane permeability assay was applied for quantifying their passive permeation, expressed as logPapp. Passive permeation was governed by the lipophilicity of the analysed compounds, and anisotropic lipophilicity was related with statistically significant passive transcellular diffusion (r2 = 0.614, P < 0.001). Moreover, experimentally determined passive permeability, logPapp, was statistically significantly associated with both in silico–predicted absorption constant, ka (r2 = 0.7886, P < 0.001), and human intestinal absorption (HIA) in percentage (r2 = 0.484, P < 0.001), respectively. However, there was no statistically significant relationship between experimentally obtained permeability on non-cellular-based model and in silico–predicted Caco-2 permeability based on the predictions conducted on two different software. Based on the obtained results, anisotropic systems are promising surrogates for determining lipophilicity, except for compounds with acidic functional groups that are completely ionized under (pH = 7.4).", journal = "Biomedical Chromatography", title = "In silico–in vitro estimation of lipophilicity and permeability association for succinimide derivatives using chromatographic anisotropic systems and parallel artificial membrane permeability assay", doi = "10.1002/bmc.5413" }
Vidović, D., Milošević, N., Pavlović, N., Todorović, N., Panić Čanji, J., Ćurčić, J., Banjac, N., Trišović, N., Božić, B.,& Lalić-Popović, M.. (2022). In silico–in vitro estimation of lipophilicity and permeability association for succinimide derivatives using chromatographic anisotropic systems and parallel artificial membrane permeability assay. in Biomedical Chromatography. https://doi.org/10.1002/bmc.5413
Vidović D, Milošević N, Pavlović N, Todorović N, Panić Čanji J, Ćurčić J, Banjac N, Trišović N, Božić B, Lalić-Popović M. In silico–in vitro estimation of lipophilicity and permeability association for succinimide derivatives using chromatographic anisotropic systems and parallel artificial membrane permeability assay. in Biomedical Chromatography. 2022;. doi:10.1002/bmc.5413 .
Vidović, Dunja, Milošević, Nataša, Pavlović, Nebojša, Todorović, Nemanja, Panić Čanji, Jelena, Ćurčić, Jelena, Banjac, Nebojša, Trišović, Nemanja, Božić, Bojan, Lalić-Popović, Mladena, "In silico–in vitro estimation of lipophilicity and permeability association for succinimide derivatives using chromatographic anisotropic systems and parallel artificial membrane permeability assay" in Biomedical Chromatography (2022), https://doi.org/10.1002/bmc.5413 . .