{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bennett JM"],"funding":["Cancer Research UK","Francis Crick Institute","NIAID NIH HHS","The Francis Crick Institute","Medical Research Council","U.S. Department of Defense","National Institutes of Health","Bill and Melinda Gates Foundation","Wellcome Trust","NIGMS NIH HHS"],"pagination":["1714-1728.e10"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11457795"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["31(9)"],"pubmed_abstract":["Malaria, caused by Plasmodium falciparum, remains a significant health burden. One major barrier for developing antimalarial drugs is the ability of the parasite to rapidly generate resistance. We previously demonstrated that salinipostin A (SalA), a natural product, potently kills parasites by inhibiting multiple lipid metabolizing serine hydrolases, a mechanism that results in a low propensity for resistance. Given the difficulty of employing natural products as therapeutic agents, we synthesized a small library of lipidic mixed alkyl/aryl phosphonates as bioisosteres of SalA. Two constitutional isomers exhibited divergent antiparasitic potencies that enabled the identification of therapeutically relevant targets. The active compound kills parasites through a mechanism that is distinct f"],"journal":["Cell chemical biology"],"pubmed_title":["Mixed alkyl/aryl phosphonates identify metabolic serine hydrolases as antimalarial targets."],"pmcid":["PMC11457795"],"funding_grant_id":["INV-033538","R33 AH27581","R01 AI141366","R01 AI109023","220318/A/20/Z","W81XWH2210520","CC2129","T32 GM113854","R01 GM145886","W81XWII2210520","R33 AI127581"],"pubmed_authors":["Yeo T","Kabeche S","Muir R","Li VL","Abegg D","Faucher F","Fidock DA","Thathy V","Bennett JM","Lovell S","Adibekian A","Yeh E","Bogyo M","Blackman MJ","Hackett F","Narwal SK"],"additional_accession":[]},"is_claimable":false,"name":"Mixed alkyl/aryl phosphonates identify metabolic serine hydrolases as antimalarial targets.","description":"Malaria, caused by Plasmodium falciparum, remains a significant health burden. One major barrier for developing antimalarial drugs is the ability of the parasite to rapidly generate resistance. We previously demonstrated that salinipostin A (SalA), a natural product, potently kills parasites by inhibiting multiple lipid metabolizing serine hydrolases, a mechanism that results in a low propensity for resistance. Given the difficulty of employing natural products as therapeutic agents, we synthesized a small library of lipidic mixed alkyl/aryl phosphonates as bioisosteres of SalA. Two constitutional isomers exhibited divergent antiparasitic potencies that enabled the identification of therapeutically relevant targets. The active compound kills parasites through a mechanism that is distinct f","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Sep","modification":"2026-06-02T09:37:40.324Z","creation":"2026-05-26T03:06:26.41Z"},"accession":"S-EPMC11457795","cross_references":{"pubmed":["39137783"],"doi":["10.1016/j.chembiol.2024.07.006"]}}