Chemoinformatics in anti-cancer chemotherapy: Multi-target QSAR model for the in silico discovery of anti-breast cancer agents

• Tipo: Artigo em Revista Científica Internacional
• Data: 2012

Autores

Alejandro Speck Planche (Autor) Outra; Valeria V Kleandrova (Autor) Outra; Feng Luan (Autor) Outra; Natalia N D S Cordeiro (Autor) FCUP

Revista

Título: European Journal of Pharmaceutical Sciences

Vol. 47

Páginas: 273-279

ISSN: 0928-0987

Editora: Elsevier

Indexação

ISI Web of Knowledge - 83 Citações

Scopus - 83 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

Outras Informações

ID Authenticus: P-002-6T8

DOI: 10.1016/j.ejps.2012.04.012

Abstract (EN): The discovery of new and more efficient anti-cancer chemotherapies is a field of research in expansion and growth. Breast cancer (BC) is one of the most studied cancers because it is the principal cause of cancer deaths in women. In the active area for the search of more potent anti-BC drugs, the use of approaches based on Chemoinformatics has played a very important role. However, until now there is no methodology able to predict anti-BC activity of compounds against more than one BC cell line, which should constitute a greater interest. In this study we introduce the first chemoinformatic multi-target (mt) approach for the in silico design and virtual screening of anti-BC agents against 13 cell lines. Here, an mt-QSAR discriminant model was developed using a large and heterogeneous database of compounds. The model correctly classified 88.47% and 92.75% of active and inactive compounds respectively, in training set. The validation of the model was carried out by using a prediction set which showed 89.79% of correct classification for active and 92.49% for inactive compounds. Some fragments were extracted from the molecules and their contributions to anti-BC activity were calculated. Several fragments were identified as potential substructural features responsible for anti-BC activity and new molecules designed from those fragments with positive contributions were suggested as possible potent and versatile anti-BC agents.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 7