Abstract (from the Book of Abstracts).
Omeprazole is a substituted benzimidazole and it presents an optically
active center with the sulfur of the sulfoxide group being the chiral center.
It is a pro-drug which can be easily converted into its respective sulfenamide
at low pH. Figure 1 shows the decomposition reaction of omeprazole (1)
to sulfenamide (4). Omeprazole has also some rotational freedom. Figure
1. Omeprazole decomposition reaction in acid medium. In this work, omeprazole
and analogue compounds have been studied against Heliobacter pylori
action. 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 These facts motivate a search to find new treatments.
Besides, some complementary studies about omeprazole behavior were performed.
Conformational aspects, racemization barriers and decomposition reaction
(Fig. 1) were taken in account. Initially, conformational analysis was
performed for all compounds. Quantum chemistry coupled to chemometric methods
PCA4 were used to find all minimum energy structures for each
drug. The PM3 semi-empirical method implemented in Gaussian 98 package
was used to perform conformational analysis and to find the racemization
barriers values. The descriptors and the total energy involved in the decomposition
reaction were calculated by using the ab initio method at Hartree-Fock
level (6-31G**), implemented in Spartan Pro package. The PLS regression
method was used to build the QSAR models.
1. B. J. Marshall, Am. J. Gastroenterol., 89 S116 (1994).
2. Y. Glupczynski, A. Burette, Am. J. Gastroenterol.,
87 1716 (1992).
3. N. Chiba, B. V. Rao, J. W. Rademaker, R. H. Hunt,
Am. J. Gastroenterol., 87 1716 (1992).
4. A. T. Bruni, B. P. Leite, M. M. C. Ferreira, J. Comp.
Chem., 23 222 (2002).
Keywords.
Keywords Plus.