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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. July 2002, Volume 1, Number 7, 339-350 |
Predicting Antifungal Activity: A Computational Screening Using Topological Descriptors
Ramon Garcia-Domenech, Ana Catala-Gregori, Carmen Calabuig, Gerardo Anton-Fos, Lucas del Castillo, and Jorge Galvez
Internet Electron. J. Mol. Des. 2002, 1, 339-350
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Abstract:
Recently, the opportunistic fungal infections have risen dramatically.
One of the biggest problems facing nowadays the antifungal therapy is
the arising of drugs resistance strains for most of the drugs currently
used in clinic practice. Therefore, it is important to find new antifungal
candidate compounds, particularly new leads, able to become the
basis for developing new drugs. Molecular topology, a formalism
based on describing the molecules as hydrogen-depleted graphs, as
well as linear discriminant analysis, a statistical tool able to distinguish
between two or more categories or objects, have been used to design
new antifungal compounds. A topological-mathematical model
comprised of two discriminant functions have been developed. The
model is able to classify correctly 98.5% of the inactive compounds
from the training set. The model validation was performed in two
ways. The first one was to check the literature sources available to
confirm the predicted antifungal activity. In the second test, for those
compounds not found in the literature, experimental tests were
performed to check the antifungal activity. A set of four compounds
was selected to be tested in the laboratory against C. albicans,
C. glabrata and S. cerevisiae. All compounds, namely anethole,
2-methyl-4,5-diphenyloxazole, 2-mercaptobenzoxazole and β-naphtyl
caproate, showed activity against the three species with MIC50
ranging between 25 and 100 μg/mL. The results confirm other
previous results from our group, regarding the usefulness of molecular
graphs and topological indices as effective tools to discover new
antifungal compounds, especially new leads.
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