{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Skinner-Adams TS"],"funding":["Medicines for Malaria Venture","U.S. Department of Health &amp; Human Services | NIH | Office of Extramural Research, National Institutes of Health","NIAID NIH HHS","Department of Health | National Health and Medical Research Council"],"pagination":["166"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6499835"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["2"],"pubmed_abstract":["Atovaquone-proguanil (Malarone®) is used for malaria prophylaxis and treatment. While the cytochrome bc1-inhibitor atovaquone has potent activity, proguanil's action is attributed to its cyclization-metabolite, cycloguanil. Evidence suggests that proguanil has limited intrinsic activity, associated with mitochondrial-function. Here we demonstrate that proguanil, and cyclization-blocked analogue tBuPG, have potent, but slow-acting, in vitro anti-plasmodial activity. Activity is folate-metabolism and isoprenoid biosynthesis-independent. In yeast dihydroorotate dehydrogenase-expressing parasites, proguanil and tBuPG slow-action remains, while bc1-inhibitor activity switches from comparatively fast to slow-acting. Like proguanil, tBuPG has activity against <i>P. berghei</i> liver-stage parasit"],"journal":["Communications biology"],"pubmed_title":["Cyclization-blocked proguanil as a strategy to improve the antimalarial activity of atovaquone."],"pmcid":["PMC6499835"],"funding_grant_id":["APP1098848","n/a","R01 AI103058","R01 AI090141"],"pubmed_authors":["Burrows JN","Wilson T","Chopra P","Andrews KT","Fidock DA","Ryan JH","von Itzstein M","Skinner-Adams TS","Jarvis KE","Clarke M","Hutt OE","Riches AG","Fisher GM","Winzeler EA","Antonova-Koch Y","Meister S"],"additional_accession":[]},"is_claimable":false,"name":"Cyclization-blocked proguanil as a strategy to improve the antimalarial activity of atovaquone.","description":"Atovaquone-proguanil (Malarone®) is used for malaria prophylaxis and treatment. While the cytochrome bc1-inhibitor atovaquone has potent activity, proguanil's action is attributed to its cyclization-metabolite, cycloguanil. Evidence suggests that proguanil has limited intrinsic activity, associated with mitochondrial-function. Here we demonstrate that proguanil, and cyclization-blocked analogue tBuPG, have potent, but slow-acting, in vitro anti-plasmodial activity. Activity is folate-metabolism and isoprenoid biosynthesis-independent. In yeast dihydroorotate dehydrogenase-expressing parasites, proguanil and tBuPG slow-action remains, while bc1-inhibitor activity switches from comparatively fast to slow-acting. Like proguanil, tBuPG has activity against <i>P. berghei</i> liver-stage parasit","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019","modification":"2025-04-19T22:56:16.414Z","creation":"2019-06-06T23:11:08Z"},"accession":"S-EPMC6499835","cross_references":{"pubmed":["31069275"],"doi":["10.1038/s42003-019-0397-3"]}}