Estudos de planejamento de ecdiesteróisdes com ação analgésica potencial: docking molecular e de farmacóforo

Abstract

The ecdysteroids are steroidal hormones present in almost all classes of arthropods and invertebrate phyla. They are analogous to phytoecdysteroids present in plants. Because of their structural similarity to human steroid compounds, many of these have hormonal or antinociceptive activity. Ecdysone is the precursor of the 20- hydroxyecysdone (20E) compound which, in turn, is an important steroid hormone that controls the embryonic development of the Arthropoda phylum. Studies report antinociceptive activity of plant extracts containing ecdysteroids. Due to this effect, it was proposed the planning and design of 60 compounds derived from 20E and the application of molecular modeling studies through molecular docking at the opioid receptors, and the study of pharmacophore. These studies were carried out in order to obtain models that allow the development of 20E derivatives with potential antinociceptive activity. The Spartan'08 software for Windows and quantum mechanics calculation methods AM1 and DFT / B3LYP with 6.31G * database were used for design, geometry optimization and conformational analysis of the compounds. The docking studies were performed using iGemdock 2.1 software. Opioid receptors μ (Mu-PDB ID: 4DKL), δ (Delta-PDB ID: 4EJ4), κ (Kappa-PDB ID: 4DJH) were downloaded from Protein Data Bank (PDB). A previous evaluation of the molecular docking allowed the selection of 12 compounds derived from 20E that may be acting with greater affinity at the opioid receptors. From this it is observed that the major interactions of the 20E derivatives at the Mu receptor occur with residues ASP- 147, HIS-297, LYS-303, TYR-148, LYS-233. At the Delta receptor at ASP-128 residues , TYR-308, TYR-129, TRP-274, TYR-308, and at the Kappa receptor at residues THR-171, ALA-175, PHE-169 and LYS-174. These data are in agrément with the literature, the interaction of these amino acid residues with the 20-hydroxyecysone compound at the Mu receptor. The pharmacophore model presented sites of hydrophobic interaction in specific spatial region that allowed its use in the selection of probable bioactive compounds.