{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:21:24Z","timestamp":1791613284808,"version":"4.3.4"},"reference-count":47,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T00:00:00Z","timestamp":1539129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:table-wrap position=\"anchor\">\n\n<jats:table frame=\"hsides\">\n<jats:col\/>\n<jats:tbody>\n<jats:tr>\n<jats:td>Hit, Lead &amp; Candidate Discovery<\/jats:td>\n<\/jats:tr>\n<\/jats:tbody>\n<\/jats:table>\n<\/jats:table-wrap><\/jats:p><jats:p>A series of 1\u2010(6\u2010methyl\u20102\u2010substituted phenyl\u20104\u2010thioxo\u20104<jats:italic>H<\/jats:italic>\u20101,3\u2010oxazin\u20105\u2010yl)ethanones <jats:bold>(3a\u2010n)<\/jats:bold> were synthesized by the reaction of benzoyl isothiocyanates with active methylene compound acetylacetone in the presence of triethyl amine in a one\u2010pot process. The structures of the products were elucidated by elemental analyses, FT\u2010IR, <jats:sup>1<\/jats:sup>H NMR, <jats:sup>13<\/jats:sup>C NMR, and mass spectroscopy. These new 1,3\u2010oxazine derivatives were evaluated for their inhibitory activity against carbonic anhydrase II. Results for in vitro assay revealed that compound <jats:bold>3b<\/jats:bold> having 4\u2010methoxy phenyl moiety was the most potent inhibitor with IC<jats:sub>50<\/jats:sub> value of 0.144\u2009\u00b1\u20090.008\u2009\u03bcM. It exhibited higher enzyme inhibitory activity as compared to the standard acetazolamide (IC<jats:sub>50<\/jats:sub>\u2009=\u20090.997\u2009\u00b1\u20090.061\u2009\u03bcM). The compounds <jats:bold>3c<\/jats:bold>, <jats:bold>3h<\/jats:bold>, and <jats:bold>3n<\/jats:bold> also displayed superior inhibitory activities compared to the rest of the synthesized oxazine derivatives. The radical scavenging activity of oxazine derivatives was also performed and it was found that compounds showed moderate antioxidant activity. Lipinski rule confirmed the therapeutic potential of the synthesized compounds. Molecular docking studies were also performed to further understand the binding affinity of these compounds with PDBID 1V9E which confirmed that the synthesized derivatives bind in the active binding site of the target protein. Based upon our results, it is proposed that compound <jats:bold>3b<\/jats:bold> may serve as a lead structure to design more potent carbonic anhydrase inhibitors.<\/jats:p>","DOI":"10.1002\/ddr.21464","type":"journal-article","created":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T03:46:23Z","timestamp":1539143183000},"page":"352-361","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Synthesis, carbonic anhydrase inhibitory activity and antioxidant activity of some 1,3\u2010oxazine derivatives"],"prefix":"10.1002","volume":"79","author":[{"given":"Rabia","family":"Qamar","sequence":"first","affiliation":[{"name":"Department of Chemistry Quaid\u2010i\u2010Azam University Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7112-9296","authenticated-orcid":false,"given":"Aamer","family":"Saeed","sequence":"additional","affiliation":[{"name":"Department of Chemistry Quaid\u2010i\u2010Azam University Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Saeed","sequence":"additional","affiliation":[{"name":"Department of Chemistry Quaid\u2010i\u2010Azam University Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6620-9080","authenticated-orcid":false,"given":"Zaman","family":"Ashraf","sequence":"additional","affiliation":[{"name":"Department of Chemistry Allama Iqbal Open University Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qamar","family":"Abbas","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Sindh Jamshoro Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mubashir","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Natural Sciences Kongju National University  Gongju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Albericio","sequence":"additional","affiliation":[{"name":"School of Chemistry and Physics University of KwaZulu\u2010Natal  Durban South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.201600183"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2011.04.040"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja061574s"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/14756366.2014.979346"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi9007512"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2010.07.069"},{"issue":"4","key":"e_1_2_7_8_1","first-page":"257","article-title":"Design, synthesis, characterization and evaluation of some 1,3\u2010oxazine derivatives as potent antimicrobial agents","volume":"5","author":"Beena K.","year":"2013","journal-title":"Scholars Research Library"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2018.05.077"},{"issue":"12","key":"e_1_2_7_10_1","first-page":"962","article-title":"Synthesis and biological evaluation of some [1,4]thiazin\u20102\u2010one and [1,4]oxazin\u20102\u2010one derivatives","volume":"45","author":"Bhat A.","year":"2008","journal-title":"Indian Drugs"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/1811199a0"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm501573b"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.22006"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909042073"},{"key":"e_1_2_7_15_1","first-page":"1999","article-title":"Bio\u2010sequestration of CO2 using carbonic anhydrase in situ encapsulated inside electrospun hollow fibers","volume":"35","author":"Cui J.","year":"2014","journal-title":"Chemical Journal of Chinese Universities"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756360902784425"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2005.12.032"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0043-123998"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm050358b"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm051256o"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/cn200100h"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543776.2018.1487400"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm801267c"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.4103\/0250-474X.38464"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2017.10.005"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2006.10.080"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.10286"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.5539\/ijc.v3n1p74"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470508169.ch5"},{"issue":"4","key":"e_1_2_7_30_1","first-page":"1123","article-title":"Tumor\u2010specific cytotoxicity and type of cell death induced by benzo[b]cyclohept[e][1,4]oxazine and 2\u2010aminotropone derivatives","volume":"29","author":"Narita T.","year":"2009","journal-title":"Anticancer Research"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2006.05.101"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2017.07.010"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20084"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2018.05.173"},{"issue":"4","key":"e_1_2_7_35_1","first-page":"320","article-title":"Anticoagulant potential of schiff bases of 1,3\u2010oxazines","volume":"4","author":"Sawant R. L.","year":"2012","journal-title":"International Journal of Pharmacy and Pharmaceutical Sciences"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2014.01.031"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161208783877820"},{"key":"e_1_2_7_38_1","volume-title":"Discovery, version 2.1","author":"Studio D.","year":"2008"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2014.05.040"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2467"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.22019"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm901524f"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2006.09.002"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2015.01.009"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol050045a"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/12030345"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg565"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.201801019"}],"container-title":["Drug Development Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fddr.21464","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.21464","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T17:42:31Z","timestamp":1760377351000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/ddr.21464"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,10]]},"references-count":47,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1002\/ddr.21464"],"URL":"https:\/\/doi.org\/10.1002\/ddr.21464","archive":["Portico"],"relation":{},"ISSN":["0272-4391","1098-2299"],"issn-type":[{"value":"0272-4391","type":"print"},{"value":"1098-2299","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,10]]},"assertion":[{"value":"2018-04-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}