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Toward of Safer Phenylbutazone Derivatives by Exploration of Toxicity Mechanism.

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.

SUBMITTER: Borges RS

PROVIDER: S-EPMC6337259 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Toward of Safer Phenylbutazone Derivatives by Exploration of Toxicity Mechanism.

Borges Rosivaldo S RS Palheta Ivanete C IC Ota Sirlene S B SSB Morais Roberto B RB Barros Valéria A VA Ramos Ryan S RS Silva Rai C RC Costa Josivan da S JDS Silva Carlos H T P CHTP Campos Joaquín M JM Santos Cleydson B R CBR

Molecules (Basel, Switzerland) 20190101 1

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 hydr ...[more]

PMID: 30609687

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Dataset Information

Toward of Safer Phenylbutazone Derivatives by Exploration of Toxicity Mechanism.

Publications

Toward of Safer Phenylbutazone Derivatives by Exploration of Toxicity Mechanism.

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