Open AccessIdentification of Novel Multifunctional Compounds for the Treatment of Some Aging Related Neurodegenerative Diseases
Author(s) -
Laura Novaroli,
Antoine Daina,
Francesca Bertolini,
Saviana Di Giovanni,
Juan Bravo,
Marianne Reist,
PierreAlain Carrupt
Publication year - 2005
Publication title -
chimia
Language(s) - English
Resource type - Journals
eISSN - 2673-2424
pISSN - 0009-4293
DOI - 10.2533/000942905777676407
Subject(s) - virtual screening , acetylcholinesterase , monoamine oxidase b , drug discovery , disease , monoamine oxidase , computational biology , pharmacology , neuroscience , bioinformatics , medicine , chemistry , biology , enzyme , biochemistry
Aging related neurodegenerative disorders such as Parkinson disease (PD) and Alzheimer's disease (AD) are the result of multiple pathophysiological pathways that contribute to the neurodegenerative cascade. Hence, multifunctional drug candidates able to interact with several targets are of great interest for the treatment of such diseases. Therefore, an experimental and virtual screening pathway to generate multifunctional hits showing promise for the treatment of PD or AD was suggested. Moreover, suitable experimental and virtual screening methods to rapidly test pre-focused compound libraries were developed and validated. In particular, the screening was focused on potential inhibitors of acetylcholinesterase (AChE) and monoamine oxidase B (MAO B) using a combination of in vitro enzymatic tests, docking and scoring approaches and refined molecular modeling tools.