{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:43:46Z","timestamp":1790189026647,"version":"4.1.0"},"reference-count":82,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,12]],"date-time":"2020-09-12T00:00:00Z","timestamp":1599868800000},"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>Non-steroidal anti-inflammatory drugs are inhibitors of cyclooxygenase-2 (COX-2) that were developed in order to avoid the side effects of non-selective inhibitors of COX-1. Thus, the present study aims to identify new selective chemical entities for the COX-2 enzyme via molecular modeling approaches. The best pharmacophore model was used to identify compounds within the ZINC database. The molecular properties were determined and selected with Pearson\u2019s correlation for the construction of quantitative structure\u2013activity relationship (QSAR) models to predict the biological activities of the compounds obtained with virtual screening. The pharmacokinetic\/toxicological profiles of the compounds were determined, as well as the binding modes through molecular docking compared to commercial compounds (rofecoxib and celecoxib). The QSAR analysis showed a fit with R = 0.9617, R2 = 0.9250, standard error of estimate (SEE) = 0.2238, and F = 46.2739, with the tetra-parametric regression model. After the analysis, only three promising inhibitors were selected, Z-964, Z-627, and Z-814, with their predicted pIC50 (\u2212log IC50) values, Z-814 = 7.9484, Z-627 = 9.3458, and Z-964 = 9.5272. All candidates inhibitors complied with Lipinski\u2019s rule of five, which predicts a good oral availability and can be used in in vitro and in vivo tests in the zebrafish model in order to confirm the obtained in silico data.<\/jats:p>","DOI":"10.3390\/molecules25184183","type":"journal-article","created":{"date-parts":[[2020,9,13]],"date-time":"2020-09-13T22:01:01Z","timestamp":1600034461000},"page":"4183","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Identification of Potential COX-2 Inhibitors for the Treatment of Inflammatory Diseases Using Molecular Modeling Approaches"],"prefix":"10.3390","volume":"25","author":[{"given":"Pedro H. F.","family":"Ara\u00fajo","sequence":"first","affiliation":[{"name":"Graduate Program in Innovation Pharmaceutical, Federal University of Amap\u00e1, 68903-419 Amap\u00e1-AP, Brazil"},{"name":"Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amap\u00e1, 68902-280 Macap\u00e1-AP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1802-1320","authenticated-orcid":false,"given":"Ryan S.","family":"Ramos","sequence":"additional","affiliation":[{"name":"Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amap\u00e1, 68902-280 Macap\u00e1-AP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0529-3714","authenticated-orcid":false,"given":"Jorddy N.","family":"da Cruz","sequence":"additional","affiliation":[{"name":"Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amap\u00e1, 68902-280 Macap\u00e1-AP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebasti\u00e3o G.","family":"Silva","sequence":"additional","affiliation":[{"name":"Campus Abaetetuba, Universidade Federal do Para, Ramal Manoel de Abreu, s\/n-Mutir\u00e3o, Abaetetuba, 68440-000 Par\u00e1, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elenilze F. B.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Graduate Program in Innovation Pharmaceutical, Federal University of Amap\u00e1, 68903-419 Amap\u00e1-AP, Brazil"},{"name":"Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amap\u00e1, 68902-280 Macap\u00e1-AP, Brazil"},{"name":"Laboratory of Organic Chemistry and Biochemistry, University of State of Amap\u00e1, 68900-070 Macap\u00e1-AP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00facio R.","family":"de Lima","sequence":"additional","affiliation":[{"name":"Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amap\u00e1, 68902-280 Macap\u00e1-AP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Williams J. C.","family":"Mac\u00eado","sequence":"additional","affiliation":[{"name":"Graduate Program in Innovation Pharmaceutical, Federal University of Amap\u00e1, 68903-419 Amap\u00e1-AP, Brazil"},{"name":"Laboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amap\u00e1, 68902-280 Macap\u00e1-AP, Brazil"},{"name":"Laboratory of Molecular Modeling and Simulation System, Federal Rural University of Amaz\u00f4nia, Rua Jo\u00e3o Pessoa, 121, Capanema, 68700-030 Par\u00e1-PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3231-1095","authenticated-orcid":false,"given":"Jos\u00e9 M.","family":"Espejo-Rom\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Biosanitary Institute of Granada (Ibs.GRANADA), Campus of Cartuja s\/n, University of Granada, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9035-8123","authenticated-orcid":false,"given":"Joaqu\u00edn M.","family":"Campos","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Biosanitary Institute of Granada (Ibs.GRANADA), Campus of Cartuja s\/n, University of Granada, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0271-335X","authenticated-orcid":false,"given":"Cleydson B. 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