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Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Review Article

Molecular Hybridization as a Tool for Designing Multitarget Drug Candidates for Complex Diseases

Author(s): Viktoriya Ivasiv, Claudia Albertini, Ana E. Gonçalves, Michele Rossi and Maria L. Bolognesi*

Volume 19, Issue 19, 2019

Page: [1694 - 1711] Pages: 18

DOI: 10.2174/1568026619666190619115735

Price: $65


Molecular hybridization is a well-exploited medicinal chemistry strategy that aims to combine two molecules (or parts of them) in a new, single chemical entity. Recently, it has been recognized as an effective approach to design ligands able to modulate multiple targets of interest. Hybrid compounds can be obtained by linking (presence of a linker) or framework integration (merging or fusing) strategies. Although very promising to combat the multifactorial nature of complex diseases, the development of molecular hybrids faces the critical issues of selecting the right target combination and the achievement of a balanced activity towards them, while maintaining drug-like-properties. In this review, we present recent case histories from our own research group that demonstrate why and how molecular hybridization can be carried out to address the challenges of multitarget drug discovery in two therapeutic areas that are Alzheimer’s and parasitic diseases. Selected examples spanning from linker- to fragment- based hybrids will allow to discuss issues and consequences relevant to drug design.

Keywords: Hybrids, Framework combination, Alzheimer's disease, Parasitic disease, Multitarget drug discovery, Fragmentbased drug discovery.

Graphical Abstract
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