RT Journal Article
T1 Toward of Safer Phenylbutazone Derivatives by Exploration of Toxicity Mechanism.
A1 Borges, Rosivaldo S
A1 Palheta, Ivanete C
A1 Ota, Sirlene S B
A1 Morais, Roberto B
A1 Barros, Valéria A
A1 Ramos, Ryan S
A1 Silva, Rai C
A1 Costa, Josivan da S
A1 Silva, Carlos H T P
A1 Campos, Joaquín M
A1 Santos, Cleydson B R
K1 DFT
K1 electron transfer
K1 metabolism
K1 phenylbutazone
K1 toxicity
AB 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.
YR 2019
FD 2019-01-01
LK http://hdl.handle.net/10668/13375
UL http://hdl.handle.net/10668/13375
LA en
DS RISalud
RD Apr 19, 2025