title: Validation of topochemical models for the prediction of permeability through the blood-brain barrier.
abstract: 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, Wiener's 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.
authors.affiliation: Faculty of Pharmaceutical Sciences, M. D. University, Rohtak-124001, India.
authors.forename: Harish
authors.initials: H
authors.lastname: Dureja
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Madan
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002199:Capillary Permeability; D020650:Combinatorial Chemistry Techniques; D003198:Computer Simulation; D015195:Drug Design; D006801:Humans; D008955:Models, Cardiovascular; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D054852:Small Molecule Libraries
chemical_list: D004364:Pharmaceutical Preparations; D054852:Small Molecule Libraries