Bruni A. T., Ferreira M. M. C., “QSAR Study of Omeprazole and Analogue Compounds as Anti Helicobacter Pylori Agents”. Caxambu, MG, Brazil, 11-16/11/2001: 1º Simpósio Brasileiro em Química Medicinal, QSAR e Modelagem Molecular: Novas Estratégias em Planejamento Racional de Fármacos [1st Brazilian Symposium on Medicinal Chemistry, QSAR and Molecular Modeling: New Approaches in Drug Design]. Poster APM12. Section: 4. Applications of Multivariate QSAR.
Omeprazole
Name
Márcia M. C. Ferreira
Institution/Company
Universidade de Campinas
Country
Brasil
First Abstract Title
QSAR Study Of Omeprazole and Analogue Compounds as Anti Helicobacter Pylori
Agents
First Abstract
Aline Thaís Bruni and Márcia Miguel Castro Ferreira
Instituto de Química, Universidade Estadual de Campinas
Campinas, SP BRAZIL 13083-970
Helicobacter pylori usually lives in the stomach and requires urease
enzyme to colonize the mucus layer.1
It plays an
important role in peptic ulcer disease, and the bacterium eradication decreases
the ulcer recurrence.2,3
These facts
motivate a search to find new treatments.
In the present work, omeprazol and analogues were studied with respect
to
their activity as inhibitors of urease
Helicobacter pylori. The experimental results were taken from Kühler
et
al.4 Conformational
analysis was performed
according to the method proposed by Bruni et al.5
(a novel methodology for systematic search coupled with PCA).
Theoretical 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 main substituents on the basic structure, dipole moment (total and
x, y, z components), HOMO and LUMO
energy, electronegativity, hardness, molecular mass, volume, area, and
ovality among others. Since several minimum
energy structures were obtained for each compound, and the calculated descriptors
showed to be sensitive to the
structural conformation, different criteria were proposed for conformation
selection. Three data sets were generated
where conformations were grouped according the minimum heat of formation,
minimum electronic energy and
structural similarity. For these three sets, experimental percent of control
was used to develop quantitative
structure-activity models by PLS method. Their crosvalidated and correlation
coefficients were very good (Q2
= 0.97
and R2 = 0.99 in average)
and the standard error of validation was much lower in comparison with
results from
literature.
References
1. B. J. Marshall, 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. Kühler, J. Fryklund, N. A. Bergaman, J. Weiliotz, A. Lee,
H. Larsson, J. Med. Chem., 38,4906 (1995).
5. A. T. Bruni, V. B. P. Leite, M. M. C. Ferreira, J. Comp. Chem. in press.
The authors acknowledge the financial support from FAPESP