{"id":13386,"date":"2023-01-11T10:25:13","date_gmt":"2023-01-11T10:25:13","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=13386"},"modified":"2024-01-11T10:26:19","modified_gmt":"2024-01-11T10:26:19","slug":"2023-design-synthesis-and-evaluation-of-novel-tetrazoles-featuring-isoxazole-moiety-as-highly-selective-antifungal-agents","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2023-design-synthesis-and-evaluation-of-novel-tetrazoles-featuring-isoxazole-moiety-as-highly-selective-antifungal-agents\/","title":{"rendered":"2023 &#8211; Design, synthesis, and evaluation of novel tetrazoles featuring isoxazole moiety as highly selective antifungal agents"},"content":{"rendered":"<p>In an effort to develop novel\u00a0azole\u00a0antifungals\u00a0with potent activity and high selectivity, a series of (2<em>R<\/em>,3<em>R<\/em>)-3-((3-substitutied-phenyl-isoxazol-5-yl)methoxy)-2-(2,4-difluorophenyl)-1-(1<em>H<\/em>-tetrazol-1-yl)butan-2-ol derivatives were designed and synthesized based on our previously work. All compounds exhibited moderate to excellent\u00a0<em>in vitro<\/em>\u00a0antifungal activities against\u00a0Candida albicans\u00a0SC5314 and\u00a0Cryptococcus neoformans\u00a0H99, but inactive against\u00a0Aspergillus fumigatus\u00a07544. Among them, the most active compound\u00a0<strong>10h<\/strong>\u00a0displayed outstanding antifungal activity against fluconazole-resistant\u00a0<em>C. albicans<\/em>\u00a0103,\u00a0<em>C. glabrata<\/em>\u00a0537 and\u00a0<em>C. auris<\/em>\u00a0922 with\u00a0MIC\u00a0values of \u22640.008\u00a0\u03bcg\/mL. In addition, compound\u00a0<strong>10h<\/strong>\u00a0was superior to FLC in inhibiting the filamentation of FLC-resistant\u00a0<em>C. albicans<\/em>\u00a0103. Notably, compound\u00a0<strong>10h<\/strong>\u00a0showed no inhibition of human\u00a0CYP3A4\u00a0with IC<sub>50<\/sub>\u00a0values of &gt;100\u00a0\u03bcM, low cytotoxicity at 32\u00a0\u03bcg\/mL and low hERG inhibition with IC<sub>50<\/sub>\u00a0values of 6.22\u00a0\u03bcM, suggesting a low risk of drug-drug interactions and good safety profiles. Furthermore, compound\u00a0<strong>10h<\/strong>\u00a0exhibited excellent PK profiles and showed remarkable\u00a0<em>in vivo<\/em>\u00a0efficacy in a mouse model of\u00a0<em>C. albicans<\/em>\u00a0and\u00a0<em>C. neoformans<\/em>\u00a0infection. Taken together, compound\u00a0<strong>10h<\/strong>\u00a0will be further investigated as a promising lead\u00a0antifungal agent.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[42],"resource_type":[75],"application_areas":[50,76],"therapeutic_areas":[54],"target_categories":[61],"target_families":[333],"targets":[92],"resource_keyword":[],"class_list":["post-13386","resource_library","type-resource_library","status-publish","hentry","products_tags-syncropatch-384","resource_type-publication","application_areas-ion-channels","application_areas-drug-discovery","therapeutic_areas-cardiac-safety-cipa","target_categories-voltage-gated-ion-channels","target_families-kv-channels","targets-kv11-1-herg"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/13386","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/media?parent=13386"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=13386"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=13386"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=13386"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=13386"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=13386"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=13386"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=13386"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=13386"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}