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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. February 2002, Volume 1, Number 2, 70-79 |
Natural Compounds with Bronchodilator Activity Selected by Molecular Topology
Imaculada Rios-Santamarina, Ramon Garcia-Domenech, Julio Cortijo, Pedro Santamaria, Esteban J. Morcillo, and Jorge Galvez
Internet Electron. J. Mol. Des. 2002, 1, 70-79
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Abstract:
The main goal of the present work is selecting new
bronchodilator lead compounds without an explicit knowledge of
their mechanism of action. This is particularly interesting since
asthma and other obstructive pulmonary diseases have become
an increasingly concerning public health problem in many
countries along the later years. The importance of the goal is
reinforced by the fact that most of the drug design currently
available methods need a previous knowledge about the
mechanism of action involved. 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 perform the task. The confirmation of the bronchodilator
activity was performed by laboratory tests on Guinea pig trachea
tissue. Several new bronchodilator-activity showing compounds
have been selected, some of them significantly more potent than
theophylline, the reference drug. Among the selected
compounds, all of them derivatives of coumarine, flavonoids and
antocianosides, stand out fisetin, an atoxic vegetal pigment
which showed 88.9% relaxation on Guinea pig isolated trachea
tissue at 0.1 mM with pD2 = 4.60, and hesperetine, (hesperidine's
aglycone), which produced a 87.4% relaxation effect at 0.1 mM
with pD2 = 5.20. As pattern drug it was used theophylline that
relaxed up to 77% at 1 mM, having pD2 = 4.69. The results
mentioned above confirms other previous results from our group,
regarding the usefulness of molecular topology as a potent tool to
discover new drugs, especially new leads, overcoming the need
for a previous knowledge on the drugs mechanism of action.
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