Atomic and molecular properties of nonclassical bioisosteric replacements of the carboxylic acid group

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8 Citations (Scopus)

Abstract

Drug design is fraught with challenges as small differences in the structure of a drug molecule can significantly affect its biological activity. Bioisosteres are interchangeably used to adjust pharmacokinetic and pharmacodynamic properties without affecting the biological activity of the drug. While electrostatic potential maps (EPMs) are typically used to show the similarity in the 'key and lock' interactions between a drug and its receptor, they are limited to qualitative comparisons. Methodology & results: Using the quantum theory of atoms in molecules, quantitative similarities among nonclassical bioisosteres of carboxylic acid were evaluated. Conclusion: The similarity in the bioisosteric groups was captured with the average electron density tool which generated remarkably close average electron densities regardless of the capping group, the isodensity values or the protonation state of the molecule. The similarities among bioisosteres was less obvious using the EPM tool.

Original languageEnglish
Pages (from-to)1111-1120
Number of pages10
JournalFuture Medicinal Chemistry
Volume12
Issue number12
DOIs
Publication statusPublished - Jun 2020
Externally publishedYes

Keywords

  • average electron densities
  • bioisosteres
  • computational chemistry and molecular modeling
  • density functional theory
  • drug design
  • electrostatic potential maps
  • quantum theory of atoms in molecules

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

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