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

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. U ovom su radu validirani i unakrsno validirani nedavno objavljeni topokemijski modeli za permeabilnost kroz krvno-moždanu barijeru. Predviđanje prolaska kroz krvno-moždanu barijeru strukturno i kemijski različitih molekula provedeno je na pet modela koji se temelje na tri topološka indeksa, Wienerovom topološkom indeksu, topološkom indeksu molekularne povezanosti i topološkom indeksu ekscentrične povezanosti. Ukupno 62 spoja podijeljena su u dva seta koji su sadržavali 31 spoj. Jedan set upotrebljen je za validaciju, a drugi za unakrsnu validaciju. Vrijednosti svih triju topoloških indeksa u početnom setu i u normaliziranom setu su računate pomoću kompjutorskog programa. Rezultati su analizirani i svakom spoju je pridružena teorijska vrijednost permeabilnosti, koja je zatim uspoređivana s