The concept of privileged structures in rational drug design: focus on acridine and quinoline scaffolds in neurodegenerative and protozoan diseases

Abstract

Introduction: For nearly 20 years, privileged structures have offered an optimal source of core scaffolds and capping fragments for the design of combinatorial libraries directed at a broad spectrum of targets. From describing structures promiscuous within a given target family, the concept has evolved to include frameworks that can modulate proteins lacking a strict target class relation.

Areas covered: Based on a literature search from 2000 to 2010, we discuss how two privileged motifs, quinolines and acridines, are particularly recurrent in compounds active against two quite different pathologies, neurodegenerative and protozoan diseases.

Expert opinion: As privileged structures, quinolines and acridines could improve the productivity of drug discovery projects in the field of neurodegenerative and protozoan diseases. They could be particularly relevant for protozoan diseases because of the importance of cost-effective strategies and less stringent intellectual property concerns. Furthermore, because of their inherent affinity for various targets, privileged structures could offer a viable starting point in the search for novel multi-target ligands. Finally, from a broader perspective, they can serve as effective probes for investigating unknown but interrelated mechanisms of action.

Keywords::

• Alzheimer's disease
• leishmaniasis
• malaria
• prion diseases
• privileged substructure
• quinacrine
• quinoline
• trypanosomiasis

Acknowledgements

The authors wish to thank G Fox for editing and proofreading the manuscript.

Notes

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