Estudo das relações entre estrutura-atividade de progestogenios contraceptivos, atraves da utilização de parametros fisico-quimicos calculados e metodos de reconhecimento de padrão

AUTOR(ES)
DATA DE PUBLICAÇÃO

1998

RESUMO

Molecular geometries of 23 17a-acetoxyprogesterones substituted and other 11 steroids were calculated with the semi-empirical method AM1. Molecular properties were calculated using the wave functions generated by AM1 as well as other computational methods. The molecular properties can be classified as: electronic, steric and hidrophobic. These parameters were analyzed by the methods of Principals Components Analysis (PCA), Hierarchical Diagram and Neural Network, in the attempt of relating them to its biological activities and pharmacological effects: oral contraceptive activity , androgenic effect, progestational activity, binding affinity for Progesterone Receptors, binding affinity for Androgenic Receptors and binding affinity for SHBG. Good correlations between the calculated parameters and the biological activities were obtained for the studied molecular groups, wich PCA as well as neural network. However, the neural network method was shown to be slightly more advantageous than Principals Components Analysis, in the classification model. PCA was found to be effective in choosing useful parameters. Parameters such ionization potential, molecular hardness, atomic charge in the position 13 of the steroidal skeleton (EET), density of the frontier electron in the positions 10 and 13 of EET, density of the frontier orbital in the position 4 of EET, density of the frontier orbital in the position 5 of EET, density of the frontier orbital in the position 9 of EET and density of the frontier radical in the position 10 of EET possesses optimum range of variation that favor certain activities or pharmacological effects. The opposite nature between progesterone and androgen receptors was verified.

ASSUNTO(S)

hormonios progestacionais anticoncepcionais orais

ACESSO AO ARTIGO

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