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Evaluation of the Usefulness of Topological Indices for Predicting Selected Physicochemical Properties of Bioactive Substances with Anti-Androgenic and Hypouricemic Activity

Due to the observed increase in the importance of computational methods in determining selected physicochemical parameters of biologically active compounds that are key to understanding their ADME/T profile, such as lipophilicity, there is a great need to work on accurate and precise in silico model...

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Autores principales: Wardecki, Dawid, Dołowy, Małgorzata, Bober-Majnusz, Katarzyna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10420683/
https://www.ncbi.nlm.nih.gov/pubmed/37570792
http://dx.doi.org/10.3390/molecules28155822
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author Wardecki, Dawid
Dołowy, Małgorzata
Bober-Majnusz, Katarzyna
author_facet Wardecki, Dawid
Dołowy, Małgorzata
Bober-Majnusz, Katarzyna
author_sort Wardecki, Dawid
collection PubMed
description Due to the observed increase in the importance of computational methods in determining selected physicochemical parameters of biologically active compounds that are key to understanding their ADME/T profile, such as lipophilicity, there is a great need to work on accurate and precise in silico models based on some structural descriptors, such as topological indices for predicting lipophilicity of certain anti-androgenic and hypouricemic agents and their derivatives, for which the experimental lipophilicity parameter is not accurately described in the available literature, e.g., febuxostat, oxypurinol, ailanthone, abiraterone and teriflunomide. Therefore, the following topological indices were accurately calculated in this paper: Gutman (M, M(ν)), Randić ((0)χ, (1)χ, (0)χ(ν), (1)χ(ν)), Wiener (W), Rouvray–Crafford (R) and Pyka (A, (0)B, (1)B) for the selected anti-androgenic drugs (abiraterone, bicalutamide, flutamide, nilutamide, leflunomide, teriflunomide, ailanthone) and some hypouricemic compounds (allopurinol, oxypurinol, febuxostat). Linear regression analysis was used to create simple linear correlations between the newly calculated topological indices and some physicochemical parameters, including lipophilicity descriptors of the tested compounds (previously obtained by TLC and theoretical methods). Our studies confirmed the usefulness of the obtained linear regression equations based on topological indices to predict ADME/T important parameters, such as lipophilicity descriptors of tested compounds with anti-androgenic and hypouricemic effects. The proposed calculation method based on topological indices is fast, easy to use and avoids valuable and lengthy laboratory experiments required in the case of experimental ADME/T studies.
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spelling pubmed-104206832023-08-12 Evaluation of the Usefulness of Topological Indices for Predicting Selected Physicochemical Properties of Bioactive Substances with Anti-Androgenic and Hypouricemic Activity Wardecki, Dawid Dołowy, Małgorzata Bober-Majnusz, Katarzyna Molecules Article Due to the observed increase in the importance of computational methods in determining selected physicochemical parameters of biologically active compounds that are key to understanding their ADME/T profile, such as lipophilicity, there is a great need to work on accurate and precise in silico models based on some structural descriptors, such as topological indices for predicting lipophilicity of certain anti-androgenic and hypouricemic agents and their derivatives, for which the experimental lipophilicity parameter is not accurately described in the available literature, e.g., febuxostat, oxypurinol, ailanthone, abiraterone and teriflunomide. Therefore, the following topological indices were accurately calculated in this paper: Gutman (M, M(ν)), Randić ((0)χ, (1)χ, (0)χ(ν), (1)χ(ν)), Wiener (W), Rouvray–Crafford (R) and Pyka (A, (0)B, (1)B) for the selected anti-androgenic drugs (abiraterone, bicalutamide, flutamide, nilutamide, leflunomide, teriflunomide, ailanthone) and some hypouricemic compounds (allopurinol, oxypurinol, febuxostat). Linear regression analysis was used to create simple linear correlations between the newly calculated topological indices and some physicochemical parameters, including lipophilicity descriptors of the tested compounds (previously obtained by TLC and theoretical methods). Our studies confirmed the usefulness of the obtained linear regression equations based on topological indices to predict ADME/T important parameters, such as lipophilicity descriptors of tested compounds with anti-androgenic and hypouricemic effects. The proposed calculation method based on topological indices is fast, easy to use and avoids valuable and lengthy laboratory experiments required in the case of experimental ADME/T studies. MDPI 2023-08-02 /pmc/articles/PMC10420683/ /pubmed/37570792 http://dx.doi.org/10.3390/molecules28155822 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wardecki, Dawid
Dołowy, Małgorzata
Bober-Majnusz, Katarzyna
Evaluation of the Usefulness of Topological Indices for Predicting Selected Physicochemical Properties of Bioactive Substances with Anti-Androgenic and Hypouricemic Activity
title Evaluation of the Usefulness of Topological Indices for Predicting Selected Physicochemical Properties of Bioactive Substances with Anti-Androgenic and Hypouricemic Activity
title_full Evaluation of the Usefulness of Topological Indices for Predicting Selected Physicochemical Properties of Bioactive Substances with Anti-Androgenic and Hypouricemic Activity
title_fullStr Evaluation of the Usefulness of Topological Indices for Predicting Selected Physicochemical Properties of Bioactive Substances with Anti-Androgenic and Hypouricemic Activity
title_full_unstemmed Evaluation of the Usefulness of Topological Indices for Predicting Selected Physicochemical Properties of Bioactive Substances with Anti-Androgenic and Hypouricemic Activity
title_short Evaluation of the Usefulness of Topological Indices for Predicting Selected Physicochemical Properties of Bioactive Substances with Anti-Androgenic and Hypouricemic Activity
title_sort evaluation of the usefulness of topological indices for predicting selected physicochemical properties of bioactive substances with anti-androgenic and hypouricemic activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10420683/
https://www.ncbi.nlm.nih.gov/pubmed/37570792
http://dx.doi.org/10.3390/molecules28155822
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