{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:04:01Z","timestamp":1785416641623,"version":"3.56.0"},"reference-count":103,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institute of Health Research","doi-asserted-by":"crossref","award":["PJT186220"],"award-info":[{"award-number":["PJT186220"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,9,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The emergence and spread of artemisinin-partial resistant, malaria-causing\n                      <jats:italic toggle=\"yes\">Plasmodium falciparum<\/jats:italic>\n                      provide the impetus for developing novel antimalarials. Pantothenamides are potent inhibitors of malaria parasite proliferation; however, their clinical use is hindered by pantetheinase-mediated degradation in human serum. Here, we report the synthesis and biological activity of a series of pantothenamide-mimics in which the thiazole ring replaces the labile amide bond with various orientations. Out of 23 novel compounds generated and tested in the presence of pantetheinase, several display sub-micromolar antiplasmodial activity\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      . A selection of compounds was studied in more detail, and CoA biosynthesis and\/or utilization pathways were confirmed to be the target. Toxicity to human cells was not observed. Kinetic studies identified the selected compounds as substrates of the\n                      <jats:italic toggle=\"yes\">Hs<\/jats:italic>\n                      PanK3 enzyme, but with much lower affinity compared to that of the natural substrate pantothenate. The most potent thiazole-bearing antiplasmodial compound was found to bind to\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      PanK with a 120-fold higher affinity compared to\n                      <jats:italic toggle=\"yes\">Hs<\/jats:italic>\n                      PanK, highlighting excellent selectivity, not only against the key first enzyme in the CoA biosynthesis pathway but also at the whole-cell level. In conclusion, thiazole substitution of the labile amide bond represents a promising avenue for developing antimalarial pantothenamide-mimics.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00331-25","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T14:04:08Z","timestamp":1755093848000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Thiazole substitution of a labile amide bond\u2014a new option toward antiplasmodial pantothenamide-mimics"],"prefix":"10.1128","volume":"69","author":[{"given":"Xiangning","family":"Liu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/019wvm592","id-type":"ROR","asserted-by":"publisher"}],"name":"Research School of Biology, Australian National University","place":["Canberra, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annica","family":"Chu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01pxwe438","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, McGill University","place":["Montreal, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Nekouei","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01pxwe438","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, McGill University","place":["Montreal, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunling Blue","family":"Lan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01pxwe438","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, McGill University","place":["Montreal, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Pierret","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01pxwe438","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, McGill University","place":["Montreal, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0933-7956","authenticated-orcid":true,"given":"Karine","family":"Auclair","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01pxwe438","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, McGill University","place":["Montreal, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3345-8440","authenticated-orcid":true,"given":"Kevin J.","family":"Saliba","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/019wvm592","id-type":"ROR","asserted-by":"publisher"}],"name":"Research School of Biology, Australian National University","place":["Canberra, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","unstructured":"World Malaria Report. 2024. Geneva World Health Organization. https:\/\/www.who.int\/teams\/global-malaria-programme\/reports\/world-malaria-report-2024."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30324-6"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/652240"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2017.88"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808859"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.EI10-0013-2016"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.22343"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-017-1809-9"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4573"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2005.04.001"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-008045382-8.00141-6"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M704610200"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.2.632-637.2005"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.17.10190"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.025312"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.2174\/187152610791163390"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2007.00093.x"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(70)90470-4"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST20140131"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054974"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006918"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.7b00024"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00603-13"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2011.02.053"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2014.06.013"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.3762\/bjoc.12.95"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.7b00240"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/ml400180d"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aas9917"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.0c00075"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-015-0673-8"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01436-16"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201800327"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41429-019-0196-6"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01755"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29688-5"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10593-012-0960-z"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01786"},{"key":"e_1_3_3_40_2","first-page":"245","volume-title":"Advances in Heterocyclic Chemistry","author":"Meanwell NA","year":"2017","unstructured":"Meanwell NA. 2017. A synopsis of the properties and applications of heteroaromatic rings in medicinal chemistry, p 245\u2013361. In Advances in Heterocyclic Chemistry. Academic Press."},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm401375q"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568026615666150915111741"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm501853m"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2015.04.015"},{"key":"e_1_3_3_45_2","first-page":"165","article-title":"Novel triazole antifungal drugs: focus on isavuconazole, ravuconazole and albaconazole","volume":"11","author":"Pasqualotto AC","year":"2010","unstructured":"Pasqualotto AC, Thiele KO, Goldani LZ. 2010. Novel triazole antifungal drugs: focus on isavuconazole, ravuconazole and albaconazole. Curr Opin Investig Drugs 11:165\u2013174.","journal-title":"Curr Opin Investig Drugs"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1086\/428839"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0101118"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-08-0999"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1997.00644.x"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.3c00913"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2015.05.047"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1039\/C8OB02812E"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0365110X63002632"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.146.3650.1474"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.304"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.359"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C500044200"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003190200"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444906012728"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00469-06"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2006.06.008"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi062299p"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701915200"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.24290"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.24841"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009797"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg026"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.08.056"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049509"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST20140096"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2010.06.006"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.748061"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3611"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.200900167"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.3109\/03602532.2011.615320"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40064-015-1082-8"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1039\/d0cb00171f"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010942200"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2013.12.010"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1002\/wcms.81"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.1002\/wcms.1606"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3943"},{"key":"e_1_3_3_83_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3235"},{"key":"e_1_3_3_84_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.4792"},{"key":"e_1_3_3_85_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.26700"},{"key":"e_1_3_3_86_2","doi-asserted-by":"publisher","DOI":"10.1002\/wcms.1510"},{"key":"e_1_3_3_87_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.8b01176"},{"key":"e_1_3_3_88_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.1c00471"},{"key":"e_1_3_3_89_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.540110311"},{"key":"e_1_3_3_90_2","doi-asserted-by":"publisher","DOI":"10.1002\/poc.685"},{"key":"e_1_3_3_91_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp0511496"},{"key":"e_1_3_3_92_2","doi-asserted-by":"publisher","DOI":"10.1021\/ct600336r"},{"key":"e_1_3_3_93_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200462213"},{"key":"e_1_3_3_94_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806129105"},{"key":"e_1_3_3_95_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja901188y"},{"key":"e_1_3_3_96_2","unstructured":"Schalkwijk J Hermkens PHH Koen Jakob D Bonnert RV. 2020. Pantothenamide analogues. WO2020141155A1 issued"},{"key":"e_1_3_3_97_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/50.5.1072"},{"key":"e_1_3_3_98_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.781840"},{"key":"e_1_3_3_99_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2009.09.005"},{"key":"e_1_3_3_100_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-396481-6.00017-9"},{"key":"e_1_3_3_101_2","doi-asserted-by":"publisher","DOI":"10.2307\/3280287"},{"key":"e_1_3_3_102_2","doi-asserted-by":"publisher","DOI":"10.1177\/1087057103256465"},{"key":"e_1_3_3_103_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01607-06"},{"key":"e_1_3_3_104_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb200366u"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00331-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00331-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T13:02:43Z","timestamp":1756904563000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00331-25"}},"subtitle":[],"editor":[{"given":"Audrey","family":"Odom John","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,3]]},"references-count":103,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9,3]]}},"alternative-id":["10.1128\/aac.00331-25"],"URL":"https:\/\/doi.org\/10.1128\/aac.00331-25","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,3]]},"assertion":[{"value":"2025-02-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00331-25"}}