Aline Thais Bruni (PG), Márcia M. C. Ferreira (PQ), Munir S. Skaf (PQ)
Instituto de Química, Universidade Estadual de Campinas
Caixa Postal 6154, CEP: 13083-970, Campinas, S.P.
 

           In this work,   a  novel  theoretical  chemistry  methodology  was  used  to  investigate
conformational  analysis  of   two  drugs:   pantoprazole  and  omeprazole.   These  drugs  are
substituted  benzimadozoles  which   suppress   acid-gastric  secretion   by   H+,  K+-ATPase
enzyme inhibition.  The number of points to be calculated is very large in a systematic  search
by conventional methods.  In proposed methodology,  the  system dimension  was  minimized
and the rotations were made in pairs of angles.  These angles are associated with the rotations
around the single bonds, as indicated by arrows in the figures. Energy surfaces were  obtained
using  AM1   semi-empirical   method   (Gaussian  94).   The  results  were  submitted   to   a
chemometric analysis.

Principal Component Analysis (PCA) was then used to find the lowest-energy conformations
for  each  molecule.   For  pantoprazole,   the   method   found   a   single  minimum  energy
conformation  (E = -4.35 kcal/mol).  For  omeprazole  two  different  energy structures were
obtained with approximately the same energy (E = 1.43 kcal/mol).  Finally, a grid search was
performed spanning the complete conformational space,  and the same results were obtained.
The number of calculation has decreased using chemometrics by 75%.

((CNPq, FAPESP)