@misc{10481/59049,
year = {2019},
month = {1},
url = {http://hdl.handle.net/10481/59049},
abstract = {A drug design for safer phenylbutazone was been explored by reactivity and docking
studies involving single electron transfer mechanism, as well as toxicological predictions. Several
approaches about its structural properties were performed through quantum chemistry calculations
at the B3LYP level of theory, together with the 6-31+G(d,p) basis sets. Molecular orbital and
ionization potential were associated to electron donation capacity. The spin densities contribution
showed a preferential hydroxylation at the para-positions of phenyl ring when compared to other
positions. In addition, on electron abstractions the aromatic hydroxylation has more impact than
alkyl hydroxylation. Docking studies indicate that six structures 1, 7, 8 and 13–15 have potential
for inhibiting human as well as murine COX-2, due to regions showing similar intermolecular
interactions to the observed for the control compounds (indomethacin and refecoxib). Toxicity can be
related to aromatic hydroxylation. In accordance to our calculations, the derivatives here proposed
are potentially more active as well safer than phenylbutazone and only structures 8 and 13–15 were
the most promising. Such results can explain the biological properties of phenylbutazone and support
the design of potentially safer candidates.},
organization = {We acknowledge the support provided by the PROPESP/UFPA and CNPq for financial support},
publisher = {MDPI},
keywords = {Phenylbutazone},
keywords = {Electron transfer},
keywords = {Metabolism},
keywords = {Toxicity},
keywords = {DFT},
title = {Toward of Safer Phenylbutazone Derivatives by Exploration of Toxicity Mechanism},
doi = {10.3390/molecules24010143},
author = {Borges, Rosivaldo S. and Campos Rosa, Joaquín María},
}