In silico–in vitro estimation of lipophilicity and permeability association for succinimide derivatives using chromatographic anisotropic systems and parallel artificial membrane permeability assay
Само за регистроване кориснике
Аутори
Vidović, DunjaMilošević, Nataša
Pavlović, Nebojša
Todorović, Nemanja
Panić, Jelena Čanji
Ćurčić, Jelena
Banjac, Nebojša
Trišović, Nemanja
Božić, Bojan
Lalić-Popović, Mladena
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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).
Кључне речи:
chromatography / in silico / lipophilicity / parallel artificial membrane permeability assayИзвор:
Biomedical Chromatography, n/a, n/a, e5413-Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200114 (Универзитет у Новом Саду, Медицински факултет) (RS-MESTD-inst-2020-200114)
URI
https://onlinelibrary.wiley.com/doi/abs/10.1002/bmc.5413http://aspace.agrif.bg.ac.rs/handle/123456789/6105
Институција/група
Poljoprivredni fakultetTY - JOUR AU - Vidović, Dunja AU - Milošević, Nataša AU - Pavlović, Nebojša AU - Todorović, Nemanja AU - Panić, Jelena Čanji AU - Ćurčić, Jelena AU - Banjac, Nebojša AU - Trišović, Nemanja AU - Božić, Bojan AU - Lalić-Popović, Mladena UR - https://onlinelibrary.wiley.com/doi/abs/10.1002/bmc.5413 UR - http://aspace.agrif.bg.ac.rs/handle/123456789/6105 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 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 IS - n/a SP - e5413 VL - n/a DO - 10.1002/bmc.5413 ER -
@article{ author = "Vidović, Dunja and Milošević, Nataša and Pavlović, Nebojša and Todorović, Nemanja and Panić, Jelena Čanji and Ćurčić, Jelena and Banjac, Nebojša and Trišović, Nemanja and Božić, Bojan and Lalić-Popović, Mladena", 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, 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", number = "n/a", pages = "e5413", volume = "n/a", doi = "10.1002/bmc.5413" }
Vidović, D., Milošević, N., Pavlović, N., Todorović, N., Panić, J. Č., 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, n/a(n/a), e5413. https://doi.org/10.1002/bmc.5413
Vidović D, Milošević N, Pavlović N, Todorović N, Panić JČ, 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.n/a(n/a):e5413. doi:10.1002/bmc.5413 .
Vidović, Dunja, Milošević, Nataša, Pavlović, Nebojša, Todorović, Nemanja, Panić, Jelena Čanji, 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, n/a, no. n/a:e5413, https://doi.org/10.1002/bmc.5413 . .