{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Desmarini D"],"funding":["NSW Health","Volkswagen Foundation","Deutsche Forschungsgemeinschaft","National Health and Medical Research Council","University of Sydney","Australian Research Council"],"pagination":["940-953"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11997995"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(4)"],"pubmed_abstract":["New antifungals are urgently needed to treat deadly fungal infections. Targeting the fungal inositol polyphosphate kinases IP<sub>3-4</sub>K (Arg1) and IP<sub>6</sub>K (Kcs1) is a promising strategy as it has been validated genetically to be crucial for fungal virulence but never pharmacologically. We now report the synthesis of <b>DT-23</b>, an analogue of <i>N</i>2-(<i>m</i>-trifluorobenzylamino)-<i>N</i>6-(<i>p</i>-nitrobenzylamino)purine (<b>TNP</b>), and demonstrate that it more potently inhibits recombinant Arg1 from the priority pathogen <i>Cryptococcus neoformans</i> (<i>Cn</i>) (IC<sub>50</sub> = 0.6 μM) than previous analogues (IC<sub>50</sub> = 10-30 μM). <b>DT-23</b> also inhibits recombinant Kcs1 with similar potency (IC<sub>50</sub> = 0.68 μM) and Arg1 and Kcs1 activity <i>in"],"journal":["ACS infectious diseases"],"pubmed_title":["Synthesis of a New Purine Analogue Class with Antifungal Activity and Improved Potency against Fungal IP&lt;sub&gt;3-4&lt;/sub&gt;K."],"pmcid":["PMC11997995"],"funding_grant_id":["APP1183939","FT220100152","APP1058779","98604","390939984"],"pubmed_authors":["Jessen H","Dinh H","Thompson PE","Cain AK","Djordjevic JT","Truong D","Sethiya P","Desmarini D","Bowring B","Liu G"],"additional_accession":[]},"is_claimable":false,"name":"Synthesis of a New Purine Analogue Class with Antifungal Activity and Improved Potency against Fungal IP&lt;sub&gt;3-4&lt;/sub&gt;K.","description":"New antifungals are urgently needed to treat deadly fungal infections. Targeting the fungal inositol polyphosphate kinases IP<sub>3-4</sub>K (Arg1) and IP<sub>6</sub>K (Kcs1) is a promising strategy as it has been validated genetically to be crucial for fungal virulence but never pharmacologically. We now report the synthesis of <b>DT-23</b>, an analogue of <i>N</i>2-(<i>m</i>-trifluorobenzylamino)-<i>N</i>6-(<i>p</i>-nitrobenzylamino)purine (<b>TNP</b>), and demonstrate that it more potently inhibits recombinant Arg1 from the priority pathogen <i>Cryptococcus neoformans</i> (<i>Cn</i>) (IC<sub>50</sub> = 0.6 μM) than previous analogues (IC<sub>50</sub> = 10-30 μM). <b>DT-23</b> also inhibits recombinant Kcs1 with similar potency (IC<sub>50</sub> = 0.68 μM) and Arg1 and Kcs1 activity <i>in","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Apr","modification":"2026-06-02T04:31:00.822Z","creation":"2026-04-14T03:13:25.901Z"},"accession":"S-EPMC11997995","cross_references":{"pubmed":["40164150"],"doi":["10.1021/acsinfecdis.4c00975"]}}