{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T13:05:19Z","timestamp":1784898319030,"version":"3.55.0"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,6,28]],"date-time":"2020-06-28T00:00:00Z","timestamp":1593302400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A new series of 1,2,3\u2010triazole\u2013(thio)barbituric acid hybrids <jats:bold>8a<\/jats:bold>\u2013<jats:bold>n<\/jats:bold> was designed and synthesized on the basis of potent pharmacophores with urease inhibitory activity. Therefore, these compounds were evaluated against <jats:italic>Helicobacter pylori<\/jats:italic> urease. The obtained result demonstrated that all the synthesized compounds, <jats:bold>8a<\/jats:bold>\u2013<jats:bold>n<\/jats:bold>, were more potent than the standard urease inhibitor, hydroxyurea. Moreover, among them, compounds <jats:bold>8a<\/jats:bold>, <jats:bold>8c<\/jats:bold>\u2013<jats:bold>e<\/jats:bold>, <jats:bold>8g<\/jats:bold>,<jats:bold>h<\/jats:bold>, and <jats:bold>8k<\/jats:bold>,<jats:bold>l<\/jats:bold> exhibited higher urease inhibitory activities than the other standard inhibitor used: thiourea. Docking studies were performed with the synthesized compounds. Furthermore, molecular dynamic simulation of the most potent compounds, <jats:bold>8e<\/jats:bold> and <jats:bold>8l<\/jats:bold>, showed that these compounds interacted with the conserved residues Cys592 and His593, which belong to the active site flap and are essential for enzymatic activity. These interactions have two consequences: (a) blocking the movement of a flap at the entrance of the active site channel and (b) stabilizing the closed active site flap conformation, which significantly reduces the catalytic activity of urease. Calculation of the physicochemical and topological properties of the synthesized compounds <jats:bold>8a<\/jats:bold>\u2013<jats:bold>n<\/jats:bold> predicted that all these compounds can be orally active. The ADME prediction of compounds <jats:bold>8a<\/jats:bold>\u2013<jats:bold>n<\/jats:bold> was also performed.<\/jats:p>","DOI":"10.1002\/ardp.202000023","type":"journal-article","created":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T06:48:32Z","timestamp":1593413312000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["New 1,2,3\u2010triazole\u2013(thio)barbituric acid hybrids as urease inhibitors: Design, synthesis, in vitro urease inhibition, docking study, and molecular dynamic simulation"],"prefix":"10.1002","volume":"353","author":[{"given":"Mohammad S.","family":"Asgari","sequence":"first","affiliation":[{"name":"School of Chemistry, College of Science University of Tehran  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Homa","family":"Azizian","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmacy\u2010International Campus Iran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Nazari Montazer","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Mohammadi\u2010Khanaposhtani","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Biology Research Center, Health Research Institute Babol University of Medical Sciences  Babol Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Asadi","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7340-0468","authenticated-orcid":false,"given":"Saghi","family":"Sepehri","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmacy Ardabil University of Medical Sciences  Ardabil Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parviz R.","family":"Ranjbar","sequence":"additional","affiliation":[{"name":"School of Chemistry, College of Science University of Tehran  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahmatollah","family":"Rahimi","sequence":"additional","affiliation":[{"name":"Department of Chemistry Iran University of Science and Technology  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmood","family":"Biglar","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bagher","family":"Larijani","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massoud","family":"Amanlou","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4171-7310","authenticated-orcid":false,"given":"Mohammad","family":"Mahdavi","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,28]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.47.5.436"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.11.009"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.1.163"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2016.1257641"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molliq.2014.03.032"},{"key":"e_1_2_5_7_1","first-page":"281","volume":"38","author":"Omar M. 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