APPLYING PHARMMAPPER SERVER AS TOOL FOR DRUG TARGET IDENTIFICATION FOR SOME DIPHENYLMETHYLPIPERAZINE AMIDES
Maya Georgieva*, Branimir Zlatkov, Alexander Zlatkov
ABSTRACT
Using the web-based tool PharmMapper, based on the reverse
pharmacophore approach, we aligned 7 newly synthesized pipreazine
amide derivatives to 2241 human protein targets, from which the top
300 targets were analyzed. By the flexible alignment of these
structures the calculated and recorded pharmacophores were obtained
and the candidate targets were prioritized, based on the corresponding
fit values and z-scores. Of high interest was the model derived for
activity to -secretase 1, since it was categorized as the probable target
for the compounds of interest. The most significant pharmacophoric
parameter was established to be the hydrophobicity of the molecule, whereas for compound
2f, with highest fit score, the significance of this parameter is greatest. It may be concluded
that structures with 4-7 hydrophobic positions and aromatic ring or four carbon atoms in the
side chain are of interest in further evaluation of piperazine bearing structures with -
secretase 1 activity.
Keywords: Alzheimer’s disease, ?-secretase 1, piperazines, synthesis, pharmacophore.
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