Title:Alzheimer: A Decade of Drug Design. Why Molecular Topology can be an Extra Edge?
Volume: 16
Issue: 6
Author(s): Riccardo Zanni, Ramon Garcia-Domenech, Maria Galvez-Llompart and Jorge Galvez*
Affiliation:
- Molecular Topology and Drug Design Unit. Department of Physical Chemistry, University of Valencia, Valencia,Spain
Keywords:
Alzheimer, molecular, topology, drug, design, QSAR.
Abstract: Background: The last decade was characterized by a growing awareness about the severity
of dementia in the field of age-related and no age-related diseases and about the importance to invest
resources in the research of new, effective treatments. Among the dementias, Alzheimer's plays a
substantial role because of its extremely high incidence and fatality. Several pharmacological
strategies have been tried but still now, Alzheimer keeps being an untreatable disease. In literature, the
number of QSAR related drug design attempts about new treatments for Alzheimer is huge, but only
few results can be considered noteworthy. Providing a detailed analysis of the actual situation and
reporting the most notable results in the field of drug design and discovery, the current review focuses
on the potential of molecular topology as a reliable tool in finding new anti-Alzheimer lead
compounds.
Methods: Published works on QSAR applied to the search of anti-Alzheimer's drugs during the last 10
years has been tracked. 2D and 3D-QSAR, HQSAR, topological indexes, etc. have been analyzed, as
well as different mechanisms of action, such as MAO, AchE, etc. An example of topological indexes’
application to the search of potential anti-Alzheimer drugs is reported.
Results: Results show that QSAR methods during the last decade represented an excellent approach to
the search of new effective drugs against Alzheimer's. In particular, QSAR based on molecular topology
allows the establishment of a direct structure-property link that results in the identification of new
hits and leads.
Conclusion: Molecular topology is a powerful tool for the discovery of new anti-Alzheimer drugs
covering simultaneously different mechanisms of action, what may help to find a definitive cure for
the disease.
