Alzheimer: A Decade of Drug Design. Why Molecular Topology can be an Extra Edge?

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.