Bruni A. T., Ferreira M. M. C., “Omeprazole and analogue compounds: A QSAR study of activity against helicobacter pylori using theoretical descriptors”. Copenhagen, Denmark, 19-23/08/2001: 7th Scandinavian Symposium on Chemometrics (SSC7), Book of Abstracts, A45 (2001). Poster P5.
Omeprazole and analogue
compounds: A QSAR
study of activity against
heliobacter
pylori using
theoretical descriptors
Aline Thaís Bruni, aline@df.ibilce.unesp.br
Márcia M. C. Ferreira, marcia@iqm.unicamp.br,
Universidade Estadual de Campinas, Instituto de Química.
Campinas, SP, 13083-970, Brazil
Keywords: Omeprazole, PLS, Hartree-Fock, QSAR
Heliobacter pylori usually lives in the stomach
and requires urease enzyme to colonize
mucus layer.1
It plays and important role in peptic ulcer disease, and the bacterium
eradication
decreases the ulcer recurrence.2,3
The facts motivate a search to find new treatments. As an
example, omeprazole and analogue have been studied against
Heliobacter
pylori action.
Kühler et al.4
presented a chemometric model to predict new compounds activity using
experimental descriptors, however most of its features
are not explicit. In present work,
omeprazole and some analogues were studied theoretically,
and the results were compared to
Kühler's.4
Theoretical descriptors were calculated for all drugs and were used to
construct a
new predictive model. Initially, conformational analysis
was performed for all compounds.
The novel methodology for systematic search coupled with
PCA was used to find all energy
minima structures for each drug. The PM3 semi-empirical
method implemented in Gaussian
98 package was used. The descriptors were calculated
by using the Hartree-Fock method at ab
initio level (6-31G**), implemented in Spartan
Pro package.
The properties used as descriptors were: electronic energy,
heat of formation, atomic charges
on the principal substituents on the basic structure,
dipole moment (total x, y, z
components), HOMO and LUMO energy, electronegativity,
hardness, molecular mass,
volume, area, and ovality among others.
The PLS regression method was used to build the QSAR models.
The obtained models are
shown to be much better suited for prediction than those
presented in the literature.4 The
theoretical descriptors included were important to improve
the models' efficiency.
The authors acknowledge the financial support from FAPESP.
References:
1. B. J. Marshall, Heliobacter pylori, Am. J. Gastroenterol.,
89,
S116 (1994).
2. Y. Glupczynski, A. Burette, Am. J. Gastroenterol.,
85,
1545 (1990).
3. N. Chiba, B. V. Rao, J. W. Rademaker, R. H. Hunt,
Am.
J. Gastroenterol., 87, 1716 (1992).
4. T. C. Kuhler, J. Fryklund, N. A. Bergaman, J. Weiliotz,
A. Lee, H. Larson, J. Med. Chem.,
38, 4906 (1995).
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