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ABSTRACT:In the present study, the aim was to select electronic properties responsible for free radical scavenging ability of a set of 25 flavonoid compounds employing chemometric methods. Electronic parameters were calculated using the AM1 semiempirical method, and chemometric methods (principal component analysis, hierarchical cluster analysis, and k-nearest neighbor) were used with the aim to build models able to find relationships between electronic features and the antioxidant activity presented by the compounds studied. According to these models, four electronic variables can be considered important to discriminate more and less antioxidant flavonoid compounds: polarizability (␣), charge at carbon 3 (QC3), total charge at substituent 5 (QS5), and total charge at substituent 3Ј (QS3Ј). The features found as being responsible for the antioxidant activity of the flavonoid compounds studied are consistent with previous results found in the literature. The results obtained can also bring improvements in the search for better antioxidant flavonoid compounds.

Métodos quimiométricos (estatísticos) são empregados para classificar um conjunto de compostos derivados de neolignanas com atividade biológica contra a Paracoccidioides brasiliensis. O método AM1 (Austin Model 1) foi utilizado para calcular um conjunto de descritores moleculares (propriedades) para os compostos em estudo. A seguir, os descritores foram analisados utilizando os seguintes métodos de reconhecimento de padrões: Análise de Componentes Principais (PCA), Análise Hierárquica de Agrupamentos (HCA) e o método de K-vizinhos mais próximos (KNN). Os métodos PCA e HCA mostraram-se bastante eficientes para classificação dos compostos estudados em dois grupos (ativos e inativos). Três descritores moleculares foram responsáveis pela separação entre os compostos ativos e inativos: energia do orbital molecular mais alto ocupado (E HOMO ), ordem de ligação entre os átomos C 1' -R 7 (L 14 ) e ordem de ligação entre os átomos C 5' -R 6 (L 22 ). Como as variáveis responsáveis pela separação entre compostos ativos e inativos são descritores eletrônicos, conclui-se que efeitos eletrônicos podem desempenhar um importante papel na interação entre receptor biológico e compostos derivados de neolignanas com atividade contra a Paracoccidioides brasiliensis.Chemometric (statistical) methods are employed to classify a set of neolignan compounds with activity against Paracoccidioides brasiliensis. The AM1 (Austin Model 1) method was used to calculate a set of molecular descriptors (properties) of the neolignan compounds under study. The descriptors were further analyzed using Principal Components Analysis (PCA), Hierarchical Cluster Analysis (HCA) and K-Nearest Neighbor (KNN) chemometric methods. The PCA and HCA methods were quite efficient to classify the compounds into two groups (active and inactive) and three descriptors were found to be important in the classification: the highest occupied molecular orbital energy (E HOMO ), the bond order between C 1' -R 7 atoms (L 14 ) and the bond order between C 5' -R 6 atoms (L 22 ). The three variables responsible for the separation between active and inactive compounds are all electronic descriptors, therefore we can conclude that electronic effects should have an important role when one is trying to understand the activity of neolignan compounds against Paracoccidioides brasiliensis.Keywords: neolignans, Paracoccidioides brasiliensis, AM1, PCA, HCA, KNN IntroductionParacoccidioides brasiliensis is a human pathogenic fungus that constitutes a major medical problem in Latin America. The microorganism is the etiological agent of paracoccioidomycosis (PCM), a systemic disease with a high incidence among the rural population of Latin America. 1 This disease is usually chronic and involves several organs and systems with predominance in the lungs which are considered as the primary site of the infection. 2 Effective treatment regimens are available to control the infectious process and most patients (60-80%) develop fibrotic sequelae that may severely hamper respiratory functions and l...