Acta Pharm. 57
(2007) 451-467
Original research paper
Validation of topochemical
models for the prediction of permeability through the blood-brain barrier
HARISH DUREJA and ANIL
KUMAR MADAN
madan_ak@yahoo.com
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, 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.
Keywords: topochemical indices, Wiener’s topochemical
index, molecular connectivity topochemical index,
eccentric connectivity topochemical index, permeability, blood-brain barrier