In silico strategies for the selection of chelating compounds with potential application in metal-promoted neurodegenerative diseases

Cristina Rodríguez-Rodríguez, Albert Rimola, Jorge Alí-Torres, Mariona Sodupe, Pilar González-Duarte

Research output: Contribution to journalArticleResearchpeer-review

12 Citations (Scopus)

Abstract

The development of new strategies to find commercial molecules with promising biochemical features is a main target in the field of biomedicine chemistry. In this work we present an in silico-based protocol that allows identifying commercial compounds with suitable metal coordinating and pharmacokinetic properties to act as metal-ion chelators in metal-promoted neurodegenerative diseases (MpND). Selection of the chelating ligands is done by combining quantum chemical calculations with the search of commercial compounds on different databases via virtual screening. Starting from different designed molecular frameworks, which mainly constitute the binding site, the virtual screening on databases facilitates the identification of different commercial molecules that enclose such scaffolds and, by imposing a set of chemical and pharmacokinetic filters, obey some drug-like requirements mandatory to deal with MpND. The quantum mechanical calculations are useful to gauge the chelating properties of the selected candidate molecules by determining the structure of metal complexes and evaluating their stability constants. With the proposed strategy, commercial compounds containing N and S donor atoms in the binding sites and capable to cross the BBB have been identified and their chelating properties analyzed. © 2010 Springer Science+Business Media B.V.
Original languageEnglish
Pages (from-to)21-30
JournalJournal of Computer-Aided Molecular Design
Volume25
Issue number1
DOIs
Publication statusPublished - 1 Jan 2011

Keywords

  • Blood brain barrier
  • DFT
  • Metal-ion chelator
  • Neurodegenerative disease
  • Virtual screening

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