<abstract xml:lang="en" xmlns="http://www.w3.org/1999/xhtml"><p>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.</p></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.

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

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

Acta Pharmaceutica

Recently published topochemical models for permeability through the blood-brain barrier were validated and cross-validated in the present study. Five models...

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

Online veröffentlicht: 28. Dez. 2007

Seitenbereich: 451 - 467

DOI: https://doi.org/10.2478/v10007-007-0036-2

Schlüsselwörter
topokemijski indeksi, Wienerov topološki indeks, topološki indeks molekularne povezanosti, topološki indeks ekscentrične povezanosti, permeabilnost, krvno-moždana barijera

This content is open access.

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

Online veröffentlicht: 28. Dez. 2007

Seitenbereich: 451 - 467

DOI: https://doi.org/10.2478/v10007-007-0036-2

Schlüsselwörtertopokemijski indeksi, Wienerov topološki indeks, topološki indeks molekularne povezanosti, topološki indeks ekscentrične povezanosti, permeabilnost, krvno-moždana barijera

This content is open access.

Schlüsselwörter
topokemijski indeksi, Wienerov topološki indeks, topološki indeks molekularne povezanosti, topološki indeks ekscentrične povezanosti, permeabilnost, krvno-moždana barijera