{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bolsakova J"],"funding":["European Regional Development Fund"],"pagination":["76-80"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10789136"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(1)"],"pubmed_abstract":["While <i>Plasmodium falciparum</i> threonyl tRNA synthetase (<i>Pf</i>ThrRS) has clearly been validated as a prospective antimalarial drug target, the number of known inhbitors of this enzyme is still limited. In order to expand the chemotypes acting as inhibitors of <i>Pf</i>ThrRS, a set of fragments were designed which incorporated bioisosteres of the <i>N</i>-acylphosphate moiety of the aminoacyladenylate as an intermediate of an enzymatic reaction. <i>N</i>-Acyl sulfamate- and <i>N</i>-acyl benzenethiazolsulfonamide-based fragments <b>9a</b> and <b>9k</b> were identified as inhibitors of the <i>Pf</i>ThrRSby biochemical assay at 100 μM concentration. These fragments were then developed into potent <i>Pf</i>ThrRS inhibitors (<b>10a</b>,<b>b</b> and <b>11</b>) by linking them with an ami"],"journal":["ACS medicinal chemistry letters"],"pubmed_title":["Discovery of Malarial Threonyl tRNA Synthetase Inhibitors by Screening of a Focused Fragment Library."],"pmcid":["PMC10789136"],"funding_grant_id":["1.1.1.1/19/A/019"],"pubmed_authors":["Parisini E","Bobrovs R","Kanepe I","Varacheva L","Rudnickiha A","Jirgensons A","Bolsakova J"],"additional_accession":[]},"is_claimable":false,"name":"Discovery of Malarial Threonyl tRNA Synthetase Inhibitors by Screening of a Focused Fragment Library.","description":"While <i>Plasmodium falciparum</i> threonyl tRNA synthetase (<i>Pf</i>ThrRS) has clearly been validated as a prospective antimalarial drug target, the number of known inhbitors of this enzyme is still limited. In order to expand the chemotypes acting as inhibitors of <i>Pf</i>ThrRS, a set of fragments were designed which incorporated bioisosteres of the <i>N</i>-acylphosphate moiety of the aminoacyladenylate as an intermediate of an enzymatic reaction. <i>N</i>-Acyl sulfamate- and <i>N</i>-acyl benzenethiazolsulfonamide-based fragments <b>9a</b> and <b>9k</b> were identified as inhibitors of the <i>Pf</i>ThrRSby biochemical assay at 100 μM concentration. These fragments were then developed into potent <i>Pf</i>ThrRS inhibitors (<b>10a</b>,<b>b</b> and <b>11</b>) by linking them with an ami","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jan","modification":"2026-06-01T22:03:19.532Z","creation":"2026-05-22T03:07:52.235Z"},"accession":"S-EPMC10789136","cross_references":{"pubmed":["38229753"],"doi":["10.1021/acsmedchemlett.3c00403"]}}