RESUMO
Molecular connectivity has been applied to the search of mathematical models able to predict the carcinogenic and teratogenic activity of a wide group of structurally heterogeneous compounds. Through the linear discriminant analysis and the diagrams of distribution of pharmacological activity, the classification criteria that minimizes the percentage of error are established. The easiness and speed of the calculation of the descriptors used in this work make the models developed useful in data bases containing a huge number of compounds.
Assuntos
Bases de Dados Factuais , Modelos Teóricos , Teratogênicos/toxicidade , Previsões , Modelos Lineares , Estrutura Molecular , Relação Estrutura-Atividade , Teratogênicos/farmacologia , Testes de ToxicidadeRESUMO
A common assumption in chemistry is that chiral behavior is associated with 3-D geometry. However, chiral information is related to symmetry, which allows the topological handling of chiral atoms by weighted graphs and the calculation of new descriptors that give a weight to the corresponding entry in the main diagonal of the topological matrix. In this study, it is demonstrated that, operating in this way, chiral topological indices are obtained that can differentiate the pharmacological activity between pairs of enantiomers. The 50% inhibitory concentration (IC50) values of the D2 dopamine receptor and the sigma receptor for a group of 3-hydroxy phenyl piperidines are specifically predicted. Moreover, the sedative character of a group of chiral barbiturates can be identified.
Assuntos
Modelos Químicos , Estereoisomerismo , Animais , Estimulantes do Sistema Nervoso Central/química , Estimulantes do Sistema Nervoso Central/farmacologia , Antagonistas dos Receptores de Dopamina D2 , Desenho de Fármacos , Hipnóticos e Sedativos/química , Hipnóticos e Sedativos/farmacologia , Técnicas In Vitro , Piperidinas/química , Piperidinas/farmacologia , Receptores sigma/antagonistas & inibidores , Relação Estrutura-AtividadeRESUMO
Molecular topology has been applied to find new lead compounds with bronchodilator activity. Among the selected compounds stands out 3-(1H-tetrazol-5yl)-9H-thioxanthene-9 -one-10,10-dioxide, anthrarobin, 9-oxo-9H-thioxantene-3-carboxylic-10,10-dioxide acid, acenocoumarol and griseofulvin, with a percentage of relaxation, at 0.1 mM, of 91, 92, 85, 69, and 74%, respectively. Theophylline shows a correspondent value of 77% (Emax = 100% at 1 mM).
