Abstract
A significant number of drugs and drug candidates in clinical development are halogenated structures. For a long time, insertion of halogen atoms on hit or lead compounds was predominantly performed to exploit their steric effects, through the ability of these bulk atoms to occupy the binding site of molecular targets. However, halogens in drug - target complexes influence several processes rather than steric aspects alone. For example, the formation of halogen bonds in ligand-target complexes is now recognized as a kind of intermolecular interaction that favorably contributes to the stability of protein-ligand complexes. This paper is aimed at introducing the fascinating versatility of halogen atoms. It starts summarizing the prevalence of halogenated drugs and their structural and pharmacological features. Next, we discuss the identification and prediction of halogen bonds in protein-ligand complexes, and how these bonds should be exploited. Interesting results of halogen insertions during the processes of hit-to-lead or lead-to-drug conversions are also detailed. Polyhalogenated anesthetics and protein kinase inhibitors that bear halogens are analyzed as cases studies. Thereby, this review serves as a guide for the virtual screening of libraries containing halogenated compounds and may be a source of inspiration for the medicinal chemists.
Keywords: Halogen bond, virtual screening, molecular docking, anesthetics, protein kinase, flavopiridol, isoflurane
Current Drug Targets
Title: Halogen Atoms in the Modern Medicinal Chemistry: Hints for the Drug Design
Volume: 11 Issue: 3
Author(s): Marcelo Zaldini Hernandes, Suellen Melo T. Cavalcanti, Diogo Rodrigo M. Moreira, Walter Filgueira de Azevedo Junior and Ana Cristina Lima Leite
Affiliation:
Keywords: Halogen bond, virtual screening, molecular docking, anesthetics, protein kinase, flavopiridol, isoflurane
Abstract: A significant number of drugs and drug candidates in clinical development are halogenated structures. For a long time, insertion of halogen atoms on hit or lead compounds was predominantly performed to exploit their steric effects, through the ability of these bulk atoms to occupy the binding site of molecular targets. However, halogens in drug - target complexes influence several processes rather than steric aspects alone. For example, the formation of halogen bonds in ligand-target complexes is now recognized as a kind of intermolecular interaction that favorably contributes to the stability of protein-ligand complexes. This paper is aimed at introducing the fascinating versatility of halogen atoms. It starts summarizing the prevalence of halogenated drugs and their structural and pharmacological features. Next, we discuss the identification and prediction of halogen bonds in protein-ligand complexes, and how these bonds should be exploited. Interesting results of halogen insertions during the processes of hit-to-lead or lead-to-drug conversions are also detailed. Polyhalogenated anesthetics and protein kinase inhibitors that bear halogens are analyzed as cases studies. Thereby, this review serves as a guide for the virtual screening of libraries containing halogenated compounds and may be a source of inspiration for the medicinal chemists.
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Cite this article as:
Hernandes Zaldini Marcelo, Cavalcanti T. Suellen Melo, Moreira M. Diogo Rodrigo, de Azevedo Junior Filgueira Walter and Leite Lima Ana Cristina, Halogen Atoms in the Modern Medicinal Chemistry: Hints for the Drug Design, Current Drug Targets 2010; 11 (3) . https://dx.doi.org/10.2174/138945010790711996
DOI https://dx.doi.org/10.2174/138945010790711996 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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