title: QSAR study of anticoccidial activity for diverse chemical compounds: prediction and experimental assay of trans-2-(2-nitrovinyl)furan.
abstract: 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.
authors.affiliation: Department of Organic Chemistry & Institute of Industrial Pharmacy, Faculty of Pharmacy, University of Santiago de Compostela, Santiago 15782, Spain. gonzalezdiazh@yahoo.es
authors.forename: Humberto
authors.initials: H
authors.lastname: González-Díaz
authors.forename: Ervelio
authors.initials: E
authors.lastname: Olazábal
authors.forename: Lourdes
authors.initials: L
authors.lastname: Santana
authors.forename: Eugenio
authors.initials: E
authors.lastname: Uriarte
authors.forename: Yenny
authors.initials: Y
authors.lastname: González-Díaz
authors.forename: Nilo
authors.initials: N
authors.lastname: Castañedo
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002645:Chickens; D003049:Coccidiostats / Q000138:chemical synthesis* / Q000494:pharmacology*; D016786:Eimeria tenella / Q000187:drug effects; D005260:Female; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology*; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D014753:Vinyl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D003049:Coccidiostats; D005663:Furans; D014753:Vinyl Compounds; C517823:trans-2-(2-nitrovinyl)furan