DesMol2, an Effective Tool for the Construction of Molecular Libraries and Its Application to QSAR Using Molecular Topology

Inma García-Pereira; Riccardo Zanni; Maria Galvez-Llompart; Jorge Galvez; Ramón García-Domenech

doi:10.3390/molecules24040736

DesMol2, an Effective Tool for the Construction of Molecular Libraries and Its Application to QSAR Using Molecular Topology

Molecules. 2019 Feb 18;24(4):736. doi: 10.3390/molecules24040736.

Authors

Inma García-Pereira¹, Riccardo Zanni², Maria Galvez-Llompart^{3

4}, Jorge Galvez⁵, Ramón García-Domenech⁶

Affiliations

¹ Institute of Robotics and Information and Communication Technologies (IRTIC), University of Valencia, 46100 Valencia, Spain. inmaculada.garcia-pereira@uv.es.
² Molecular Topology and Drug Design Unit, Department of Physical Chemistry, University of Valencia, Avenida V.A. Estelles s/n, Burjassot, 46100 Valencia, Spain. riccardo.zanni@uv.es.
³ Molecular Topology and Drug Design Unit, Department of Physical Chemistry, University of Valencia, Avenida V.A. Estelles s/n, Burjassot, 46100 Valencia, Spain. maria.galvez@uv.es.
⁴ Microbiology and Plant Pathology-Unit (CSIC Associated), Department of Microbiology, Faculty of Sciences, University of Malaga, 29071 Malaga, Spain. maria.galvez@uv.es.
⁵ Molecular Topology and Drug Design Unit, Department of Physical Chemistry, University of Valencia, Avenida V.A. Estelles s/n, Burjassot, 46100 Valencia, Spain. Jorge.galvez@uv.es.
⁶ Molecular Topology and Drug Design Unit, Department of Physical Chemistry, University of Valencia, Avenida V.A. Estelles s/n, Burjassot, 46100 Valencia, Spain. ramon.garcia@uv.es.

Abstract

A web application, DesMol2, which offers two main functionalities, is presented: the construction of molecular libraries and the calculation of topological indices. These functionalities are explained through a practical example of research of active molecules to the formylpeptide receptor (FPR), a receptor associated with chronic inflammation in systemic amyloidosis and Alzheimer's disease. Starting from a data(base) of 106 dioxopiperazine pyrrolidin piperazine derivatives and their respective constant values of binding affinity to FPR, multilinear regression and discriminant analyses are performed to calculate several predictive topological-mathematical models. Next, using the DesMol2 application, a molecular library consisting of 6,120 molecules is built and performed for each predictive model. The best potential active candidates are selected and compared with results from other previous works.

Keywords: Alzheimer’s disease; DesMol2; linear discriminant analysis; molecular libraries; multilinear regression analysis; topology descriptors.

MeSH terms

Databases, Chemical
Drug Discovery
Models, Molecular*
Molecular Structure
Piperazine / chemistry
Protein Binding
Quantitative Structure-Activity Relationship*
Receptors, Formyl Peptide / chemistry
Small Molecule Libraries / chemistry*
Software*

Substances

Receptors, Formyl Peptide
Small Molecule Libraries
Piperazine