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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. December 2008, Volume 7, Number 12, 260-273 |
Application of Molecular Topology to Predict the Inhibition of
Trypanosoma cruzi Cruzain by Thiosemicarbazones
Ramón García-Domenech, Luciana Barbosa, Matilde Lacarra, Mauricio Salazar, and Jorge Gálvez
Internet Electron. J. Mol. Des. 2008, 7, 260-273
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Abstract:
The main goal of the present work is finding a classification mathematical
model of the inhibitory activity against T. cruzi cruzain through molecular
topology. This is particularly interesting since the finding of new
therapeutic alternatives for Chagas disease continues to be a very
difficult task as demonstrated by the low number of lead drugs approved
by the international agencies in the later years in this field.
Molecular topology, a formalism based on describing the molecules
as hydrogen-depleted graphs, as well as linear discriminant analysis,
a statistical tool capable to distinguish between two or more categories
or objects, have been used to the search of new active compounds by
virtual screening throughout databases. Linear discriminant analysis
has been developed with a group of thiosemicarbazone and semicarbazone
derivates. A mathematical model comprised of one discriminant function
has been selected. The model is able to classify correctly 92.8% of
the compounds from the training set. We have built up a virtual
library with several hundreds of thiosemicarbazone derivatives for
virtually seeking and optimizing the inhibitory activity against
T. cruzi cruzain. Molecular topology has been successfully used
to find a QSAR model classification the inhibitory activity against
T. cruzi cruzain of a group of thiosimicarbazone and semicarbazone derivates.
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