کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1365118 | 981552 | 2007 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: QSAR study of anticoccidial activity for diverse chemical compounds: Prediction and experimental assay of trans-2-(2-nitrovinyl)furan QSAR study of anticoccidial activity for diverse chemical compounds: Prediction and experimental assay of trans-2-(2-nitrovinyl)furan](/preview/png/1365118.png)
In this work we report a QSAR model that discriminates between chemically heterogeneous classes of anticoccidial and non-anticoccidial compounds. For this purpose we used the Markovian Chemicals in silico Design (MARCH-INSIDE) approach J. Mol. Mod.2002, 8, 237–245; J. Mol. Mod.2003, 9, 395–407]. Linear discriminant analysis allowed us to fit the discriminant function. This function correctly classifies 86.67% of anticoccidial compounds and 96.23% of inactive compounds in the training series. Overall classification is 94.12%. We validated the model by means of an external predicting series, with 86.96% of global predictability. Remarkably, the present model is based on topological as well as configuration-dependent molecular descriptors. Therefore, the model performs timely calculations and allows discrimination between Z/E and chiral isomers. Finally, to exemplify the use of the model in practice we report the prediction and experimental assay of trans-2-(2-nitrovinyl)furan. It is notable that lesion control was 72.86% at mg/kg of body weight with respect to 60% at 125 mg/kg for amprolium (control drug). The back-projection map for this compound predicts a high level of importance for the double bond and for the nitro group in the trans position. We conclude that the MARCH-INSIDE approach enables the accurate fast track identification of anticoccidial hits. Moreover, trans-2-(2-nitrovinyl)furan seems to be a promising drug for the treatment of coccidiosis.
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Journal: Bioorganic & Medicinal Chemistry - Volume 15, Issue 2, 15 January 2007, Pages 962–968