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Design of a multi-target focused library for antidiabetic targets using a comprehensive set of chemical transformation rules

Virtual small molecule libraries are valuable resources for identifying bioactive compounds in virtual screening campaigns and improving the quality of libraries in terms of physicochemical properties, complexity, and structural diversity. In this context, the computational-aided design of libraries...

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Autores principales: Saldívar-González, Fernanda I., Navarrete-Vázquez, Gabriel, Medina-Franco, José L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651762/
https://www.ncbi.nlm.nih.gov/pubmed/38027021
http://dx.doi.org/10.3389/fphar.2023.1276444
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author Saldívar-González, Fernanda I.
Navarrete-Vázquez, Gabriel
Medina-Franco, José L.
author_facet Saldívar-González, Fernanda I.
Navarrete-Vázquez, Gabriel
Medina-Franco, José L.
author_sort Saldívar-González, Fernanda I.
collection PubMed
description Virtual small molecule libraries are valuable resources for identifying bioactive compounds in virtual screening campaigns and improving the quality of libraries in terms of physicochemical properties, complexity, and structural diversity. In this context, the computational-aided design of libraries focused against antidiabetic targets can provide novel alternatives for treating type II diabetes mellitus (T2DM). In this work, we integrated the information generated to date on compounds with antidiabetic activity, advances in computational methods, and knowledge of chemical transformations available in the literature to design multi-target compound libraries focused on T2DM. We evaluated the novelty and diversity of the newly generated library by comparing it with antidiabetic compounds approved for clinical use, natural products, and multi-target compounds tested in vivo in experimental antidiabetic models. The designed libraries are freely available and are a valuable starting point for drug design, chemical synthesis, and biological evaluation or further computational filtering. Also, the compendium of 280 transformation rules identified in a medicinal chemistry context is made available in the linear notation SMIRKS for use in other chemical library enumeration or hit optimization approaches.
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spelling pubmed-106517622023-11-02 Design of a multi-target focused library for antidiabetic targets using a comprehensive set of chemical transformation rules Saldívar-González, Fernanda I. Navarrete-Vázquez, Gabriel Medina-Franco, José L. Front Pharmacol Pharmacology Virtual small molecule libraries are valuable resources for identifying bioactive compounds in virtual screening campaigns and improving the quality of libraries in terms of physicochemical properties, complexity, and structural diversity. In this context, the computational-aided design of libraries focused against antidiabetic targets can provide novel alternatives for treating type II diabetes mellitus (T2DM). In this work, we integrated the information generated to date on compounds with antidiabetic activity, advances in computational methods, and knowledge of chemical transformations available in the literature to design multi-target compound libraries focused on T2DM. We evaluated the novelty and diversity of the newly generated library by comparing it with antidiabetic compounds approved for clinical use, natural products, and multi-target compounds tested in vivo in experimental antidiabetic models. The designed libraries are freely available and are a valuable starting point for drug design, chemical synthesis, and biological evaluation or further computational filtering. Also, the compendium of 280 transformation rules identified in a medicinal chemistry context is made available in the linear notation SMIRKS for use in other chemical library enumeration or hit optimization approaches. Frontiers Media S.A. 2023-11-02 /pmc/articles/PMC10651762/ /pubmed/38027021 http://dx.doi.org/10.3389/fphar.2023.1276444 Text en Copyright © 2023 Saldívar-González, Navarrete-Vázquez and Medina-Franco. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Saldívar-González, Fernanda I.
Navarrete-Vázquez, Gabriel
Medina-Franco, José L.
Design of a multi-target focused library for antidiabetic targets using a comprehensive set of chemical transformation rules
title Design of a multi-target focused library for antidiabetic targets using a comprehensive set of chemical transformation rules
title_full Design of a multi-target focused library for antidiabetic targets using a comprehensive set of chemical transformation rules
title_fullStr Design of a multi-target focused library for antidiabetic targets using a comprehensive set of chemical transformation rules
title_full_unstemmed Design of a multi-target focused library for antidiabetic targets using a comprehensive set of chemical transformation rules
title_short Design of a multi-target focused library for antidiabetic targets using a comprehensive set of chemical transformation rules
title_sort design of a multi-target focused library for antidiabetic targets using a comprehensive set of chemical transformation rules
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651762/
https://www.ncbi.nlm.nih.gov/pubmed/38027021
http://dx.doi.org/10.3389/fphar.2023.1276444
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