Premium
Molecular topology as novel strategy for Alzheimer's disease drug discovery
Author(s) -
Pasinetti Giulio Maria
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.894.5
Subject(s) - drug discovery , topology (electrical circuits) , dual (grammatical number) , disease , computational biology , drug , characterization (materials science) , drug target , computer science , neuroscience , biology , nanotechnology , medicine , bioinformatics , mathematics , pharmacology , materials science , art , literature , pathology , combinatorics
Molecular topology (MT) uses and expands upon the principles governing molecular connectivity theory of numerically characterizing the molecular structure of, in the present case, active anti‐Alzheimer's disease (AD) drugs/agents using topological descriptors to build models. Topological characterization has been shown to embody sufficient molecular information to provide a strong correlation to therapeutic efficacy. In the present study, we used MT to include multiple bioactive properties to identify multifunctional single agent compounds, in this case, the dual functions of Aβ –lowering and anti‐oligomerization. Using this technology, we identified and designed novel compounds in chemical classes unrelated to current anti‐AD agents that exert dual Aβ lowering and anti‐Aβ oligomerization activities in animal models of AD. AD is a multifaceted disease with different pathological features. Our study for the first time demonstrated that MT can provide a novel strategy in designing molecules that target multiple pathological mechanisms of AD.