Abstract

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 reversepharmacophore approach, we aligned 7 newly synthesized pipreazineamide derivatives to 2241 human protein targets, from which the top300 targets were analyzed. By the flexible alignment of thesestructures the calculated and recorded pharmacophores were obtainedand the candidate targets were prioritized, based on the correspondingfit values and z-scores. Of high interest was the model derived foractivity to -secretase 1, since it was categorized as the probable targetfor the compounds of interest. The most significant pharmacophoricparameter was established to be the hydrophobicity of the molecule, whereas for compound2f, with highest fit score, the significance of this parameter is greatest. It may be concludedthat structures with 4-7 hydrophobic positions and aromatic ring or four carbon atoms in theside chain are of interest in further evaluation of piperazine bearing structures with -secretase 1 activity.

Keywords: Alzheimer’s disease, ?-secretase 1, piperazines, synthesis, pharmacophore.