Structure-activity study of combretastin and derivatives / Estudo estrutura-atividade da combretastina e derivados

AUTOR(ES)
DATA DE PUBLICAÇÃO

2007

RESUMO

Combretastatin, a stilbene isolated in 80 s, has been widely studied by the pharmaceutical industry due to its promising anticarcinogenic action. As an antineoplastic agent it acts interrupting the polymerization-depolymerization cycle of the microtubules, an important cellular component to motility, strutuctural maintenance and cellular mitosis. Its main feature consists in dissociate the microtubules in endothelial cells of the tumoral vascular system, leading to disruption of the blood ow that feeds the carcinomas. One of the great advantages of Combretastatin, when compared with others compounds, is the fact that it does not lead to drug resistance in chemotherapy treatments. We investigated the structure of Combretastatin and 17 derivatives using semiempirical methods. We performed the study of the relationship between theoretical properties and experimental activity of these molecules using three pattern recognition methodologies: Electronic Index Methodology (EIM), Principal Component Analysis (PCA) and Hierarchical Clusters Analysis (HCA). For each methodology we found rules and patterns capable of classifying our molecules into active or inactive, using the properties theoretically calculated. The results obtained from the three methodologies confirm the applicability of the EIM and reinforce the importance of the electronic variables for the classi cation of the biological activity of Combretastatins

ASSUNTO(S)

electronic structure quimica quantica estrutura eletronica structure-activity relationships (biochemistry) relação estrutura-atividade (bioquimica) quantum chemistry

ACESSO AO ARTIGO

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