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

Alya A. Arabi, Zayed University

ORCID Identifiers

0000-0003-3664-314X

Document Type

Article

Source of Publication

Future Medicinal Chemistry

Publication Date

6-1-2020

Abstract

© 2020 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.

ISSN

1756-8919

Publisher

Future Medicine Ltd.

Volume

12

Issue

12

First Page

1111

Last Page

1120

Disciplines

Chemistry | Life Sciences | Medicine and Health Sciences

Keywords

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

Scopus ID

85087465269

Indexed in Scopus

yes

Open Access

no

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