Document Detail

Rational drug design for anti-cancer chemotherapy: Multi-target QSAR models for the in silico discovery of anti-colorectal cancer agents.
MedLine Citation:
PMID:  22750007     Owner:  NLM     Status:  Publisher    
The discovery of new and more potent anti-cancer agents constitutes one of the most active fields of research in chemotherapy. Colorectal cancer (CRC) is one of the most studied cancers because of its high prevalence and number of deaths. In the current pharmaceutical design of more efficient anti-CRC drugs, the use of methodologies based on Chemoinformatics has played a decisive role, including Quantitative-Structure-Activity Relationship (QSAR) techniques. However, until now, there is no methodology able to predict anti-CRC activity of compounds against more than one CRC cell line, which should constitute the principal goal. In an attempt to overcome this problem we develop here the first multi-target (mt) approach for the virtual screening and rational in silico discovery of anti-CRC agents against ten cell lines. Here, two mt-QSAR classification models were constructed using a large and heterogeneous database of compounds. The first model was based on linear discriminant analysis (mt-QSAR-LDA) employing fragment-based descriptors while the second model was obtained using artificial neural networks (mt-QSAR-ANN) with global 2D descriptors. Both models correctly classified more than 90% of active and inactive compounds in training and prediction sets. Some fragments were extracted from the molecules and their contributions to anti-CRC activity were calculated using mt-QSAR-LDA model. Several fragments were identified as potential substructural features responsible for the anti-CRC activity and new molecules designed from those fragments with positive contributions were suggested and correctly predicted by the two models as possible potent and versatile anti-CRC agents.
Alejandro Speck-Planche; Valeria V Kleandrova; Feng Luan; M Natália D S Cordeiro
Related Documents :
17139207 - Enriching the portrait: methodological triangulation of life-closing theory.
17697567 - An approach to the study of dynamics of work motivation using the diary method.
20204937 - What is an adequate sample size? operationalising data saturation for theory-based inte...
23028927 - Boundary conditions for heat transfer and evaporative cooling in the trachea and air sa...
24856507 - An appropriate and systematized procedure for validating qualitative methods: its appli...
15005537 - A model to assess the risk of the introduction into japan of the bovine spongiform ence...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-15
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  -     ISSN:  1464-3391     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-7-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
REQUIMTE/Department of Chemistry and Biochemistry, University of Porto, Porto 4169-007, Portugal.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Osteoblast-specific transcription factor Osterix (Osx) and HIF-1? cooperatively regulate gene expres...
Next Document:  Synthesis, antimalarial activity and cytotoxicity of 10-aminoethylether derivatives of artemisinin.