{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T14:20:43Z","timestamp":1782915643586,"version":"3.54.5"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T00:00:00Z","timestamp":1550102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"DOI":"10.3389\/fcimb.2019.00009","type":"journal-article","created":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T04:25:30Z","timestamp":1550118330000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Novel Synthetic Polyamines Have Potent Antimalarial Activities in vitro and in vivo by Decreasing Intracellular Spermidine and Spermine Concentrations"],"prefix":"10.3389","volume":"9","author":[{"given":"Kamal","family":"El Bissati","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Redel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Min","family":"Ting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph D.","family":"Lykins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"McPhillie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajendra","family":"Upadhya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick M.","family":"Woster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel","family":"Yarlett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kami","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis M.","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2019,2,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1016\/S1473-3099(12)70181-0","article-title":"Artemisinin-resistant Plasmodium falciparum in Pursat province, Western Cambodia: a parasite clearance rate study","volume":"12","author":"Amaratunga","year":"2012","journal-title":"Lancet Infect. Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1042\/bj2220815","article-title":"Polyamine levels and the activity of their biosynthetic enzymes in human erythrocytes infected with the malarial parasite, Plasmodium falciparum","volume":"222","author":"Assaraf","year":"1984","journal-title":"Biochem. J."},{"key":"B3","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1111\/j.1550-7408.2001.tb00327.x","article-title":"Polyamine synthesis and interconversion by the microsporidian Encephalitozoon cuniculi","volume":"48","author":"Bacchi","year":"2001","journal-title":"J. Eukaryot. Microbiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1126\/science.6775372","article-title":"Polyamine metabolism: a potential therapeutic target in trypanosomes","volume":"210","author":"Bacchi","year":"1980","journal-title":"Science"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1099\/mic.0.26889-0","article-title":"Polyamine metabolism in a member of the phylum Microspora (Encephalitozoon cuniculi): effects of polyamine analogues","volume":"150","author":"Bacchi","year":"2004","journal-title":"Microbiology"},{"key":"B6","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1128\/AAC.46.1.55-61.2002","article-title":"Novel synthetic polyamines are effective in the treatment of experimental microsporidiosis, an opportunistic AIDS-associated infection","volume":"46","author":"Bacchi","year":"2002","journal-title":"Antimicrob. Agents Chemother."},{"key":"B7","doi-asserted-by":"publisher","first-page":"3229","DOI":"10.1016\/j.bmcl.2006.03.048","article-title":"Novel alkylpolyaminoguanidines and alkylpolyaminobiguanides with potent antitrypanosomal activity","volume":"16","author":"Bi","year":"2006","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B8","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1073\/pnas.86.2.651","article-title":"Bis(benzyl)polyamine analogs inhibit the growth of chloroquine-resistant human malaria parasites (Plasmodium falciparum) in vitro and in combination with alpha-difluoromethylornithine cure murine malaria","volume":"86","author":"Bitonti","year":"1989","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B9","doi-asserted-by":"publisher","first-page":"S49","DOI":"10.1007\/s00436-002-0766-5","article-title":"Eflornithine for the treatment of human African trypanosomiasis","volume":"90","author":"Burri","year":"2003","journal-title":"Parasitol. Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/nrd2243","article-title":"Targeting polyamine metabolism and function in cancer and other hyperproliferative diseases","volume":"6","author":"Casero","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"B11","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1007\/s00726-009-0424-7","article-title":"Functional consequences of perturbing polyamine metabolism in the malaria parasite, Plasmodium falciparum","volume":"38","author":"Clark","year":"2010","journal-title":"Amino Acids"},{"key":"B12","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1128\/AAC.16.6.710","article-title":"Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique","volume":"16","author":"Desjardins","year":"1979","journal-title":"Antimicrob. Agents Chemother."},{"key":"B13","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1056\/NEJMoa0808859","article-title":"Artemisinin resistance in Plasmodium falciparum malaria","volume":"361","author":"Dondorp","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.jmb.2007.07.053","article-title":"Crystal structure of Plasmodium falciparum spermidine synthase in complex with the Substrate decarboxylated S-adenosylmethionine and the potent inhibitors 4MCHA and AdoDATO","volume":"373","author":"Dufe","year":"2007","journal-title":"J. Mol. Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.pt.2013.05.002","article-title":"Artemisinin resistance in Plasmodium falciparum: what is it really?","volume":"29","author":"Ferreira","year":"2013","journal-title":"Trends Parasitol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"4586","DOI":"10.1021\/jm030175u","article-title":"Cyclopropane-containing polyamine analogues are efficient growth inhibitors of a human prostate tumor xenograft in nude mice","volume":"46","author":"Frydman","year":"2003","journal-title":"J. Med. Chem."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2857","DOI":"10.1128\/AAC.49.7.2857-2864.2005","article-title":"3-Aminooxy-1-Aminopropane and derivatives have an antiproliferative effect on cultured Plasmodium falciparum by decreasing intracellular polyamine concentrations","volume":"49","author":"Gupta","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"B18","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/j.molbiopara.2005.04.004","article-title":"The spermidine synthase of the malaria parasite Plasmodium falciparum: molecular and biochemical characterisation of the polyamine synthesis enzyme","volume":"142","author":"Haider","year":"2005","journal-title":"Mol. Biochem. Parasitol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1021\/acs.jctc.5b00864","article-title":"OPLS3: a force field providing broad coverage of drug-like small molecules and proteins","volume":"12","author":"Harder","year":"2015","journal-title":"J. Chem. Theory Comput."},{"key":"B20","doi-asserted-by":"publisher","first-page":"12077","DOI":"10.1021\/ja00105a068","article-title":"Structural effects in novel steroidal polyamine-DNA binding","volume":"116","author":"Hsieh","year":"1994","journal-title":"J. Am. Chem. Soc."},{"key":"B21","doi-asserted-by":"publisher","first-page":"2769","DOI":"10.3389\/fmicb.2019.00009","article-title":"A novel polyamine analog inhibits growth and induces apoptosis in human breast cancer cells","volume":"9","author":"Huang","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1006\/bbrc.2000.2601","article-title":"Polyamines: mysterious modulators of cellular functions","volume":"271","author":"Igarashi","year":"2000","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B23","doi-asserted-by":"publisher","first-page":"418","DOI":"10.2307\/3280287","article-title":"Synchronization of Plasmodium falciparum erythrocytic stages in culture","volume":"65","author":"Lambros","year":"1979","journal-title":"J. Parasitol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"205","DOI":"10.4269\/ajtmh.1993.48.205","article-title":"Measurement of the lactate dehydrogenase activity of Plasmodium falciparum as an assessment of parasitemia","volume":"48","author":"Makler","year":"1993","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"B25","doi-asserted-by":"publisher","first-page":"739","DOI":"10.4269\/ajtmh.1993.48.739","article-title":"Parasite lactate dehydrogenase as an assay for Plasmodium falciparum drug sensitivity","volume":"48","author":"Makler","year":"1993","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"B26","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1146\/annurev.pa.35.040195.000415","article-title":"Polyamines as targets for therapeutic intervention","volume":"35","author":"Marton","year":"1995","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1016\/S1471-4922(01)01908-0","article-title":"Targeting polyamines of parasitic protozoa in chemotherapy","volume":"17","author":"M\u00fcller","year":"2001","journal-title":"Trends Parasitol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"8097","DOI":"10.1074\/jbc.275.11.8097","article-title":"In the human malaria parasite Plasmodium falciparum, polyamines are synthesized by a bifunctional ornithine decarboxylase, S-adenosylmethionine decarboxylase","volume":"275","author":"M\u00fcller","year":"2000","journal-title":"J. Biol. Chem."},{"key":"B29","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1093\/nar\/4.3.685","article-title":"Polyamine induced aggregation of DNA","volume":"4","author":"Osland","year":"1977","journal-title":"Nucleic Acids Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"C212","DOI":"10.1152\/ajpcell.1982.243.5.C212","article-title":"Polyamine metabolism and function","volume":"243","author":"Pegg","year":"1982","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1960","DOI":"10.1016\/S0140-6736(12)60484-X","article-title":"Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study","volume":"379","author":"Phyo","year":"2012","journal-title":"Lancet Lond. Engl."},{"key":"B32","doi-asserted-by":"publisher","first-page":"4723","DOI":"10.1021\/jm980172v","article-title":"Conformationally restricted analogues of 1N,12N-bisethylspermine: synthesis and growth inhibitory effects on human tumor cell lines","volume":"41","author":"Reddy","year":"1998","journal-title":"J. Med. Chem."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e0163442","DOI":"10.1371\/journal.pone.0163442","article-title":"Binding and inhibition of spermidine synthase from Plasmodium falciparum and implications for in vitro inhibitor testing","volume":"11","author":"Sprenger","year":"2016","journal-title":"PLoS ONE"},{"key":"B34","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1107\/S1399004714027011","article-title":"Three-dimensional structures of Plasmodium falciparum spermidine synthase with bound inhibitors suggest new strategies for drug design","volume":"71","author":"Sprenger","year":"2015","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"B35","first-page":"1440","article-title":"Effects of polyamine depletion on proliferation and differentiation of murine erythroleukemia cells","volume":"44","author":"Sugiura","year":"1984","journal-title":"Cancer Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1126\/science.781840","article-title":"Human malaria parasites in continuous culture","volume":"193","author":"Trager","year":"1976","journal-title":"Science"},{"key":"B37","doi-asserted-by":"publisher","first-page":"4121","DOI":"10.1016\/S0968-0896(03)00453-X","article-title":"Long-chain polyamines (oligoamines) exhibit strong cytotoxicities against human prostate cancer cells","volume":"11","author":"Valasinas","year":"2003","journal-title":"Bioorg. Med. Chem."},{"key":"B38","doi-asserted-by":"publisher","first-page":"4635","DOI":"10.1074\/jbc.M807085200","article-title":"Co-inhibition of Plasmodium falciparum S-adenosylmethionine decarboxylase\/ornithine decarboxylase reveals perturbation-specific compensatory mechanisms by transcriptome, proteome, and metabolome analyses","volume":"284","author":"van Brummelen","year":"2009","journal-title":"J. Biol. Chem."},{"key":"B39","doi-asserted-by":"publisher","first-page":"5131","DOI":"10.1016\/j.bmc.2015.01.036","article-title":"Interrogating alkyl and arylalkylpolyamino (bis)urea and (bis)thiourea isosteres as potent antimalarial chemotypes against multiple lifecycle forms of Plasmodium falciparum parasites","volume":"23","author":"Verlinden","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"B40","doi-asserted-by":"publisher","first-page":"6624","DOI":"10.1021\/jm200463z","article-title":"Discovery of novel alkylated (bis)urea and (bis)thiourea polyamine analogues with potent antimalarial activities","volume":"54","author":"Verlinden","year":"2011","journal-title":"J. Med. Chem."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/bj20031327","article-title":"A perspective of polyamine metabolism","volume":"376","author":"Wallace","year":"2003","journal-title":"Biochem. J."},{"key":"B42","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1126\/science.1155165","article-title":"Qinghaosu (artemisinin): the price of success","volume":"320","author":"White","year":"2008","journal-title":"Science"},{"key":"B43","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/B.978-0-7020-5101-2.00044-3","article-title":"Malaria","volume":"383","author":"White","year":"2014","journal-title":"Lancet"},{"key":"B44","volume-title":"World Health Organization Malaria Report","year":"2015"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.1016\/S0960-894X(01)00315-8","article-title":"Novel alkylpolyamine analogues that possess both antitrypanosomal and antimicrosporidial activity","volume":"11","author":"Zou","year":"2001","journal-title":"Bioorg. Med. Chem. Lett."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fcimb.2019.00009\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T04:25:32Z","timestamp":1550118332000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fcimb.2019.00009\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,14]]},"references-count":45,"alternative-id":["10.3389\/fcimb.2019.00009"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2019.00009","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,14]]},"article-number":"9"}}