{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T20:52:38Z","timestamp":1780347158283,"version":"3.54.1"},"reference-count":69,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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\u201315 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\u201315 were the most promising. Such results can explain the biological properties of phenylbutazone and support the design of potentially safer candidates.<\/jats:p>","DOI":"10.3390\/molecules24010143","type":"journal-article","created":{"date-parts":[[2019,1,3]],"date-time":"2019-01-03T03:36:30Z","timestamp":1546486590000},"page":"143","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Toward of Safer Phenylbutazone Derivatives by Exploration of Toxicity Mechanism"],"prefix":"10.3390","volume":"24","author":[{"given":"Rosivaldo S.","family":"Borges","sequence":"first","affiliation":[{"name":"N\u00facleo de Estudos e Sele\u00e7\u00e3o de Mol\u00e9culas Bioativas\u2014NESBio, College of Pharmacy, Health Sciences Institute, Federal University of Par\u00e1, Bel\u00e9m 66075-110, PA, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Qu\u00edmica Medicinal e Modelagem Molecular, Health Science Institute, Federal University of Par\u00e1, Bel\u00e9m 66075-110, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivanete C.","family":"Palheta","sequence":"additional","affiliation":[{"name":"N\u00facleo de Estudos e Sele\u00e7\u00e3o de Mol\u00e9culas Bioativas\u2014NESBio, College of Pharmacy, Health Sciences Institute, Federal University of Par\u00e1, Bel\u00e9m 66075-110, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirlene S. 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