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