Unified QSAR & Network-Based Computational Chemistry Approach to Antimicrobials. II. Multiple Distance and Triadic Census Analysis of Antiparasitic Drugs Complex Networks

• Tipo: Artigo em Revista Científica Internacional
• Data: 2010

Autores

Francisco J Prado Prado (Autor) Outra; Florencio M Ubeira (Autor) Outra; Fernanda Borges (Autor) FCUP; Humberto Gonzalez Diaz (Autor) Outra

Revista

Título: Journal of Computational Chemistry

Vol. 31

ISSN: 0192-8651

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 42 Citações

Scopus - 45 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Química

Outras Informações

ID Authenticus: P-003-9QQ

Abstract (EN): In the previous work, we reported a multitarget Quantitative Structure-Activity Relationship (mt-QSAR) model to predict drug activity against different fungal species. This mt-QSAR allowed us to construct a drug-drug multispecies Complex Network (msCN) to investigate drug-drug similarity (Gonzalez-Diaz and Prado-Prado, J Comput Chem 2008, 29, 656). However, important methodological points remained unclear, such as follows: (1) the accuracy of the methods when applied to other problems; (2) the effect of the distance type used to construct the msCN; (3) how to perform the inverse procedure to study species-species similarity with multidrug resistance CNs (mdrCN); and (4) the implications and necessary steps to perform a substructural Triadic Census Analysis (TCA) of the msCN. To continue the present series with other important problem, we developed here a mt-QSAR model for more than 700 drugs tested in the literature against different parasites (predicting antiparasitic drugs). The data were processed by Linear Discriminate Analysis (LDA) and the model classifies correctly 93.62% (1160 out of 1239 cases) in training. The model validation was carried out by means of external predicting series, the model classified 573 out of 607, that is, 94.4% of cases. Next, we carried out the first comparative study of the topology of six different drug-drug msCNs based on six different distances such as Euclidean, Chebychev, Manhattan, etc. Furthermore, we compared the selected drug-drug msCN and species-species mdsCN with random networks. We also introduced here the inverse methodology to construct species-species msCN based on a mt-QSAR model. Last, we reported the first substructural analysis of drug-drug msCN using Triadic Census Analysis (TCA) algorithm. (c) 2009 Wiley Periodicals, Inc. J Comput Chem 31: 164-173, 2010

Idioma: Inglês

Tipo (Avaliação Docente): Científica