A Structure-Activity Relationship (SAR) Study of Neolignan Compounds with Anti-schistosomiasis Activity

Abstract

Um conjunto de dezoito compostos de neolignanas com atividade antiesquistossomose foi estudado com o método semi-empírico PM3 e outros métodos teóricos com o intuito de avaliar algumas propriedades (variáveis ou descritores) moleculares selecionadas e correlacioná-las com a atividade biológica.Análise exploratória dos dados (análise de componentes principais, PCA, e análise hierárquica de agrupamentos, HCA), análise discriminante (DA) e o método KNN foram utilizados na obtenção de possíveis correlações entre os descritores calculados e a atividade biológica em questão e na predição da atividade antiesquistossimose de algumas moléculas teste. Os descritores moleculares responsáveis pela separação entre os compostos ativos e inativos foram: energia de hidratação (HE), refratividade molecular (MR) e carga sobre o átomo C19 (Q 19 ). Estes descritores fornecem informações a respeito do tipo de interação que pode ocorrer entre os compostos e seu respectivo receptor biológico. Após a construção do modelo para compostos ativos e inativos, os métodos PCA, HCA, DA e KNN foram empregados em um estudo de predição. Foram estudados 10 novos compostos e somente 5 deles foram classificados como ativos contra esquistossomose.A set of eighteen neolignan derivative compounds with anti-schistosomiasis activity was studied by using the quantum mechanical semi-empirical method PM3 and other theoretical methods in order to calculate selected molecular properties (variables or descriptors) to be correlated to their biological activities.Exploratory data analysis (principal component analysis, PCA, and hierarchical cluster analysis, HCA), discriminant analysis (DA) and the Kth nearest neighbor (KNN) method were employed for obtaining possible relationships between the calculated descriptors and the biological activities studied and predicting the anti-schistosomiasis activity of new compounds from a test set. The molecular descriptors responsible for the separation between active and inactive compounds were: hydration energy (HE), molecular refractivity (MR) and charge on the C19 carbon atom (Q 19 ). These descriptors give information on the kind of interaction that can occur between the compounds and their respective biological receptor. The prediction study was done with a new set of ten derivative compounds by using the PCA, HCA, DA and KNN methods and only five of them were predicted as active against schistosomiasis.

Levels of As, Cd, Pb and Hg found in the hair from people living in Altamira, Pará, Brazil: environmental implications in the Belo Monte area

“…32 Three general aspects can be attained when PCA analysis is employed: (i) the original set of variables can be reduced to a smaller set that accounts for most of the variance in the data set; (ii) PCA can search the data for qualitative and quantitative distinctions in situations where the number of data available is quite large; (iii) PCA can be used to test hypotheses about the qualitative and quantitative distinctions in the data set. [15][16][17][18]33,34 …”

“…[15][16][17][18] Principal component analysis (PCA), hierarchical cluster analysis (HCA) and discriminant analysis (DA) methods were used in the statistical treatment of the data to build a model to make possible the classification of these residents according to the amounts of As, Cd, Pb and Hg in their hair. This type of procedure has been quite successful in similar studies [19][20][21][22] with trace levels of chemical elements present in hair samples, and for distinction among persons diagnosed with cancer.…”

Computational modelling of the antischistosomal activity for neolignan derivatives based on the MIA-SAR approach

“…A dataset consisting of 18 neolignans with reported activity against S. mansoni cercaria in rats was employed (see Table 1) [19]. The neolignans are dimers formed from oxidative coupling of allyl and propenil phenols that occur in the Myristicaceae family of plants.…”

Effects of the antimycobacterial compound 2-phenoxy-1-phenylethanone on rat hepatocytes and formation of metabolites

“…Natural neolignans have been isolated from Virola surinamensis and found to be effective against Schistosoma mansoni (Barata et al, 1978). In studies covering infectious diseases, neolignan analogues were synthesized (Barata et al, 1978;Aveniente et al, 2007) and shown to have antimicrobial activity against Leishmania (Barata et al, 2000), Schistosoma (Alves et al, 2002), fungi (Lima et al, 1987) and Mycobacterium tuberculosis H37Rv (De Souza et al, 2011). The most effective analogue, 2-phenoxy-1-phenylethanone (LS-2), showed promising extra-and intracellular antimycobacterial activity and very weak cytotoxicity against V79 cells, J774 macrophages and rat hepatocytes.…”