首页|In silico–in vitro estimation of lipophilicity and permeability association for succinimide derivatives using chromatographic anisotropic systems and parallel artificial membrane permeability assay

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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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).

chromatographyin silicolipophilicityparallel artificial membrane permeability assay

Dunja Vidovi?、Nata?a Milo?evi?、Neboj?a Pavlovi?、Nemanja Todorovi?、Jelena ?anji Pani?、Jelena ?ur?i?、Neboj?a Banjac、Nemanja Tri?ovi?、Bojan Bo?i?、Mladena Lali?‐Popovi?

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Department of Pharmacy,Faculty of Medicine, University of Novi Sad

Faculty of Pharmacy,University Business Academy in Novi Sad

Faculty of Agriculture, Food Technology and Biochemistry,University of Belgrade

Faculty of Technology and Metallurgy,University of Belgrade

Faculty of Biology, Institute of Physiology and Biochemistry “Ivan Djaja”,University of Belgrade

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2022

10.1002/bmc.5413

Biomedical Chromatography

Biomedical Chromatography

EISCI
ISSN：0269-3879
年,卷(期)：2022.36(9)
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