{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:22:25Z","timestamp":1790821345349,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T00:00:00Z","timestamp":1592784000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2020,7,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Fungal infections are a global issue affecting over 150 million people worldwide annually, with 750\u2009000 of these caused by invasive\n                    <jats:italic>Candida<\/jats:italic>\n                    infections. Azole drugs are the frontline treatment against fungal infections; however, resistance to current azole antifungals in\n                    <jats:italic>C. albicans<\/jats:italic>\n                    poses a threat to public health. Two series of novel azole derivatives, short and extended derivatives, have been designed, synthesised and investigated for CYP51 inhibitory activity, binding affinity and minimum inhibitory concentration (MIC) against\n                    <jats:italic>C. albicans<\/jats:italic>\n                    strains. The short derivatives were more potent against the\n                    <jats:italic>C. albicans<\/jats:italic>\n                    strains (e.\u2009g., MIC 2\u2010(4\u2010chlorophenyl)\u2010\n                    <jats:italic>N<\/jats:italic>\n                    \u2010(2,4\u2010dichlorobenzyl)\u20103\u2010(1\n                    <jats:italic>H<\/jats:italic>\n                    \u2010imidazol\u20101\u2010yl)propanamide (\n                    <jats:bold>5\u2009f<\/jats:bold>\n                    ) &lt;0.03\u2005\u03bcg\/mL,\n                    <jats:italic>N<\/jats:italic>\n                    \u2010(4\u2010((4\u2010chlorophenyl)sulfonamido)benzyl)\u20102\u2010phenyl\u20103\u2010(1\n                    <jats:italic>H<\/jats:italic>\n                    \u20101,2,4\u2010triazol\u20101\u2010yl)propanamide (\n                    <jats:bold>12\u2009c<\/jats:bold>\n                    ), 1\u2005\u03bcg\/mL, fluconazole 0.125\u2005\u03bcg\/mL) but both displayed comparable enzyme binding and inhibition (\n                    <jats:bold>5\u2009f<\/jats:bold>\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>d<\/jats:sub>\n                    62\u00b117\u2005nM, IC\n                    <jats:sub>50<\/jats:sub>\n                    0.46\u2005\u03bcM;\n                    <jats:bold>12\u2009c<\/jats:bold>\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>d<\/jats:sub>\n                    43\u00b118\u2005nM, IC\n                    <jats:sub>50<\/jats:sub>\n                    0.33\u2005\u03bcM, fluconazole\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>d<\/jats:sub>\n                    41\u00b113\u2005nM, IC\n                    <jats:sub>50<\/jats:sub>\n                    0.31\u2005\u03bcM, posaconazole\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>d<\/jats:sub>\n                    43\u00b111\u2005nM, IC\n                    <jats:sub>50<\/jats:sub>\n                    0.2\u2005\u03bcM). The short series had poor selectivity for CaCYP51 over the human homologue, whereas the selectivity of the extended series, for example, compound\n                    <jats:bold>12\u2009c<\/jats:bold>\n                    , was higher (21.5\u2010fold) than posaconazole (4.7\u2010fold) based on\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>d<\/jats:sub>\n                    values, although posaconazole was more selective (615\u2010fold) than\n                    <jats:bold>12\u2009c<\/jats:bold>\n                    (461\u2010fold) based on IC\n                    <jats:sub>50<\/jats:sub>\n                    values. Based on inhibitory activity and selectivity profile, the extended series are the better of the two series for further development.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202000250","type":"journal-article","created":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T09:00:50Z","timestamp":1590570050000},"page":"1294-1309","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Small\u2010Molecule Inhibitors Targeting Sterol 14\u03b1\u2010Demethylase (CYP51): Synthesis, Molecular Modelling and Evaluation Against\n                    <i>Candida albicans<\/i>"],"prefix":"10.1002","volume":"15","author":[{"given":"Faizah A.","family":"Binjubair","sequence":"first","affiliation":[{"name":"School of Pharmacy &amp; Pharmaceutical Sciences Cardiff University  King Edward VII Avenue Cardiff CF10 3NB UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josie E.","family":"Parker","sequence":"additional","affiliation":[{"name":"Centre for Cytochrome P450 Biodiversity Institute of Life Science Swansea University  Swansea SA2 8PP UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G.","family":"Warrilow","sequence":"additional","affiliation":[{"name":"Centre for Cytochrome P450 Biodiversity Institute of Life Science Swansea University  Swansea SA2 8PP UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalika","family":"Puri","sequence":"additional","affiliation":[{"name":"School of Pharmacy &amp; Pharmaceutical Sciences Cardiff University  King Edward VII Avenue Cardiff CF10 3NB UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Braidley","sequence":"additional","affiliation":[{"name":"School of Pharmacy &amp; Pharmaceutical Sciences Cardiff University  King Edward VII Avenue Cardiff CF10 3NB UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esra","family":"Tatar","sequence":"additional","affiliation":[{"name":"School of Pharmacy &amp; Pharmaceutical Sciences Cardiff University  King Edward VII Avenue Cardiff CF10 3NB UK"},{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy Marmara University  34668 Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven L.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Centre for Cytochrome P450 Biodiversity Institute of Life Science Swansea University  Swansea SA2 8PP UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane E.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Centre for Cytochrome P450 Biodiversity Institute of Life Science Swansea University  Swansea SA2 8PP UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9487-1100","authenticated-orcid":false,"given":"Claire","family":"Simons","sequence":"additional","affiliation":[{"name":"School of Pharmacy &amp; 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