Descriptor-and fragment-based QSAR models for a series of Schistosoma mansoni purine nucleoside inhibitors

Journal of the Brazilian Chemical Society

Andricopulo, Adriano D¹  Freitas, Humberto F¹  Universidade de São Paulo, São Carlos, Brazil¹  Postigo, Matheus P¹  Universidade Federal da Bahia, Salvador, Brazil¹  Castilho, Marcelo S¹ 

关键词: purine nucleoside phosphorylase;    schistosomiasis;    fragment-based;    descriptors;    QSAR;   

DOI  :  10.1590/S0103-50532011000900014

学科分类：化学（综合）

来源: SciELO

【 摘 要 】

The enzyme purine nucleoside phosphorylase from Schistosoma mansoni (SmPNP) is an attractive molecular target for the treatment of major parasitic infectious diseases, with special emphasis on its role in the discovery of new drugs against schistosomiasis, a tropical disease that affects millions of people worldwide. In the present work, we have determined the inhibitory potency and developed descriptor- and fragment-based quantitative structure-activity relationships (QSAR) for a series of 9-deazaguanine analogs as inhibitors of SmPNP. Significant statistical parameters (descriptor-based model: r2 = 0.79, q2 = 0.62, r2pred = 0.52; and fragment-based model: r2 = 0.95, q2 = 0.81, r2pred = 0.80) were obtained, indicating the potential of the models for untested compounds. The fragment-based model was then used to predict the inhibitory potency of a test set of compounds, and the predicted values are in good agreement with the experimental results.

【 授权许可】

Unknown