Pereira F. S., Medeiros W. R., Pasqualoto K. F. M., Ferreira M. M. C., "APPLICATION OF UNSUPERVISED CHEMOMETRICS METHODS TO A SET OF INHIBITORS OF ESCHERICHIA COLI ENOYL-ACP REDUCSTASE, FABI". Ribeirão Preto, SP, Brazil, 25-28/09/2005: 5th International Congress of Pharmaceutical Sciences (CIFARP2005), Braz. J. Pharm. Sci., 41(Suppl 1) (2005), 269. Poster MM009. Section: Molecular Modeling (MM).
MM001-APPLICATION
OF UNSUPERVISED CHEMOMETRICS METHODS
TO A SET OF INHIBITORS OF ESCHERICHIA
COLI ENOYL-ACP REDUCSTASE, FABI
FLÁVIA DA SILVA PEREIRA1 (PG); WALKÍRIA RÉGIS DE MEDEIROS1 (PG); KERLY FERNANDA MESQUITA PASQUALOTO1 (PQ); MÁRCIA MIGUEL CASTRO FERREIRA1 (PQ)
1UNICAMP
Introduction: The important structural element
of diazaborines is a heterocyclic 1,2-diazine ring containing
a boron as a third hetero
atom. Purpose: Selection of the descriptors
calculated from a set of fifty-one diazaborine derivatives based
on their relationship with
the biological activity data. Methodology:
Three-dimensional models of diazaborine analogues in their neutral
forms were built using
two crystallographic structures as geometry reference.
Partial atomic charges were computed employing the
AM1 semipempirical
method. Energy minimization and
molecular dynamic simulations (MDSs) were carried out
(MOLSIM 3.2). The lowest energy
conformer for each of ligand from the MDSs was used to
obtain the descriptors. Principal component analysis (PCA) and hierarchical
cluster analysis (HCA) were used to treat the calculated
descriptors. Results: Three sample groups are showin in the HCA.
According
the PCA, the partial atomic
charges of the 1,2-diazine ring are
seemingly important contributions to the
biological activity.
Perspectives: Apply the receptor-independent
(RI) 4D-QSAR formalism to this set of diazaborines
for predicting the interaction
pharmacophoric elements (IPEs) as well as the alignment
in the FabI active site.
Financial Support: CNPq
Supervisor: Márcia Miguel Castro Ferreira.