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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Bibliographic Details
Published inFrontiers in pharmacology Vol. 14; p. 1276444
Main Authors Saldívar-González, Fernanda I, Navarrete-Vázquez, Gabriel, Medina-Franco, José L
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 2023
Subjects
computer-aided drug design
diabetes
library enumeration
ligandbased design
multi-target design
target-focused libraries
target-focused libraries
library enumeration
multi-target design
ligandbased design
transformation rules
computer-aided drug design
diabetes
reaction informatics
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Summary: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 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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ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2023.1276444