Acta Pharm. 57 (2007) 451-467

full paper

Original research paper


Validation of topochemical models for the prediction of permeability through the blood-brain barrier



Faculty of Pharmaceutical Sciences, M. D. University, Rohtak-124001, India

Accepted September 7, 2007


Recently published topochemical models for permeability through the blood-brain barrier were validated and cross-validated in the present study. Five models based on three topochemical indices, Wienerís topochemical index - a distance-based topochemical descriptor, molecular connectivity topochemical index - an adjacency-based topochemical descriptor and eccentric connectivity topochemical index - an adjacency-cum-distance based topochemical descriptor, for permeability of structurally and chemically diverse molecules through blood-brain barrier were used in the present investigation. A data set comprising 62 structurally and chemically diverse compounds was selected. This data set was divided into two sets of 31 compounds each - one to serve as the validation set and other as the cross-validation set. The values of all the three-topochemical indices in the original as well as in the normalized form for each of the 31 compounds of the validation set were computed using an in house computer program. Resultant data was analyzed and each compound was assigned a permeability characteristic using topochemical models, which was then compared with the reported permeability through the blood-brain barrier. Accuracy of prediction of these models was calculated. The same procedure was similarly followed for the cross-validation set. Studies revealed accuracy of prediction of the order of 70-80% during validation. Surprisingly, very high predictability of the order of 77-91% was observed during cross-validation. High predictability observed during validation as well as cross-validation authenticates topochemical models for prediction of permeability through the blood-brain barrier.


Keywords: topochemical indices, Wienerís topochemical index, molecular connectivity topochemical index, eccentric connectivity topochemical index, permeability, blood-brain barrier