Structure-Activity Relationship of Compounds which are Anti-Schistosomiasis Active

Abstract

O método do orbital molecular AM1 foi empregado para calcular um conjunto de descritores moleculares para vinte neolignanas sintéticas com atividade anti-esquistossomose. O método de reconhecimento de padrão (análise de componentes principais ACP, análise de conglomerados AC e análise de discriminante) foi utilizado para obter a relação entre a estrutura molecular e a atividade biológica. O conjunto de moléculas foi classificado em dois grupos de acordo com seus graus de atividade biológica. Estes resultados permitem que, projete-se racionalmente novos compostos, potenciais candidatos à síntese e à avaliação biológica.The molecular orbital method AM1 was employed to calculate a set of molecular descriptors for twenty synthetic neolignan derivatives with anti-schistosomiasis activity. The pattern recognition method (principal component analysis PCA and cluster analysis CA and discriminant analysis methods) have been employed to obtain the relationship between the molecular descriptors and biological activity. The set of molecules was classified into two groups according to their degree of biological activity. These results allow us to rationally project new compounds, potential candidates for synthesis and biological evaluation.

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

“…8 Among many descriptors (variables) that have been utilized in SAR studies, [9][10][11] we have chosen the following descriptors to be evaluated: HOMO -The energy of the highest occupied molecular orbital (eV); LUMO -The energy of the lowest unoccupied molecular orbital (eV); χ -Mulliken's electronegativity (eV); POL -Molecular polarizability (a.u. ); Q N -Net atomic charge on atom N; t -Torsional angle (see Figure 1); d -bond angle (see Figure 1); HE -Hydration energy (kcal mol -1 ); MR -Molecular refractivity (Å 3 ); VOL -Molecular volume (Å 3 ); Log P -Partition coefficient.…”

A study of neolignan compounds with biological activity against Paracoccidioides brasiliensis by using quantum chemical and chemometric methods

“…From the results obtained with the three chemometric (statistical) methods (PCA, HCA and KNN), we can see that the variables responsible for the separation between active and inactive compounds, i.e. E HOMO , L 14 and L 22 , are all electronic variables. Therefore we can conclude that electronic effects should have an important role when one is trying to understand the activity of neolignan compounds against P. brasiliensis.…”

“…This correlation is known as structure-activity relationship (SAR) [18][19][20][21] and many of such studies have been reported in the literature. [22][23][24] The SAR methods have been used with success in pharmaceutical applications, 25 and in this work we calculated the following molecular properties to be correlated with the biological activity under study: log P: the values of this property were obtained from the hydrophobic parameters of the substituents by using the molecular package Spartan 5.0; 26 …”

“…After several analyses, the best separation was obtained by using the following variables: E HOMO , L 14 and L 22 , whose calculated values are presented in Table 1. This suggests that the other variables are not significant for the classification of the compounds studied.…”

“…E HOMO , L 14 and L 22 , are all electronic variables. Therefore we can conclude that electronic effects should have an important role when one is trying to understand the activity of neolignan compounds against P. brasiliensis.…”