{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:10:52Z","timestamp":1790089852331,"version":"4.0.1"},"reference-count":35,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2015,8,4]],"date-time":"2015-08-04T00:00:00Z","timestamp":1438646400000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology , Ministry of Science and Technology","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001501","name":"University Grants Commission","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100001501","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,10,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Malaria continues to be a major health problem globally. There is an urgent need to find new antimalarials. Acriflavine (ACF) is known as an antibacterial agent and more recently as an anticancer agent. Here, we report that ACF inhibits the growth of asexual stages of both chloroquine (CQ) sensitive and resistant strains of human malarial parasite, Plasmodium falciparum in vitro at nanomolar concentration. ACF clears the malaria infection in vivo from the bloodstreams of mice infected with Plasmodium berghei. Interestingly, ACF is accumulated only in the parasitized red blood cells (RBCs) and parasite specific transporters may have role in this specific drug accumulation. We further show that ACF impairs DNA replication foci formation in the parasites and affects the enzymatic activities of apicoplast specific Gyrase protein. We thus establish ACF as a potential antimalarial amidst the widespread incidences of drug resistant Plasmodium strains.<\/jats:p>","DOI":"10.1021\/cb500476q","type":"journal-article","created":{"date-parts":[[2014,8,4]],"date-time":"2014-08-04T11:24:26Z","timestamp":1407151466000},"page":"2366-2373","source":"Crossref","is-referenced-by-count":51,"title":["Potent Antimalarial Activity of Acriflavine\n                    <i>In Vitro<\/i>\n                    and\n                    <i>In Vivo<\/i>"],"prefix":"10.1021","volume":"9","author":[{"given":"Srikanta","family":"Dana","sequence":"first","affiliation":[{"name":"Jawaharlal Nehru University , , ,","place":["New Delhi, India, 110067"]},{"name":"Jawaharlal Nehru University , , ,","place":["New Delhi, India, 110067"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhaneswar","family":"Prusty","sequence":"additional","affiliation":[{"name":"Jawaharlal Nehru University , , ,","place":["New Delhi, India, 110067"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devender","family":"Dhayal","sequence":"additional","affiliation":[{"name":"National Institute of Malaria Research , ,","place":["New Delhi, India, 110077"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohit Kumar","family":"Gupta","sequence":"additional","affiliation":[{"name":"Jawaharlal Nehru University , , ,","place":["New Delhi, India, 110067"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraf","family":"Dar","sequence":"additional","affiliation":[{"name":"Jawaharlal Nehru University , , ,","place":["New Delhi, India, 110067"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sobhan","family":"Sen","sequence":"additional","affiliation":[{"name":"Jawaharlal Nehru University , , ,","place":["New Delhi, India, 110067"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pritam","family":"Mukhopadhyay","sequence":"additional","affiliation":[{"name":"Jawaharlal Nehru University , , ,","place":["New Delhi, India, 110067"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tridibesh","family":"Adak","sequence":"additional","affiliation":[{"name":"National Institute of Malaria Research , ,","place":["New Delhi, India, 110077"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman Kumar","family":"Dhar","sequence":"additional","affiliation":[{"name":"Jawaharlal Nehru University , , ,","place":["New Delhi, India, 110067"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,8,4]]},"reference":[{"key":"2026090205152385700_cit1","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1126\/science.1102452","article-title":"Targeting\nmalaria virulence and remodeling proteins to the host erythrocyte","volume":"306","author":"Marti","year":"2004","journal-title":"Science"},{"key":"2026090205152385700_cit2","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/261585a0","article-title":"Genetics\nof chloroquine resistance in malaria parasites","volume":"261","author":"Rosario","year":"1976","journal-title":"Nature"},{"key":"2026090205152385700_cit3","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1056\/NEJMoa0808859","article-title":"Artemisinin\nresistance in Plasmodium falciparum malaria","volume":"361","author":"Dondorp","year":"2009","journal-title":"N.\nEngl. J. Med."},{"key":"2026090205152385700_cit4","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1056\/NEJMc0805011","article-title":"Evidence of artemisinin-resistant\nmalaria in western Cambodia","volume":"359","author":"Noedl","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"2026090205152385700_cit5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jac\/47.1.1","article-title":"Acridine\u2500A\nneglected antibacterial chromophore","volume":"47","author":"Wainwright","year":"2001","journal-title":"J. Antimicrob.\nChemother."},{"key":"2026090205152385700_cit6","doi-asserted-by":"crossref","first-page":"17910","DOI":"10.1073\/pnas.0909353106","article-title":"Acriflavine inhibits HIF-1 dimerization,\ntumor growth,\nand vascularization","volume":"106","author":"Lee","year":"2009","journal-title":"Proc. Natl. Acad. Sci.\nU.S.A."},{"key":"2026090205152385700_cit7","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1136\/bmj.1.4289.341","article-title":"Aminoacridine\ncompounds as surface antiseptics","volume":"1","author":"Browning","year":"1943","journal-title":"Br. Med. J."},{"key":"2026090205152385700_cit8","doi-asserted-by":"crossref","first-page":"13302","DOI":"10.1074\/jbc.272.20.13302","article-title":"acrB mutation located\nat carboxyl-terminal region of\ngyrase B subunit reduces DNA binding of DNA gyrase","volume":"272","author":"Funatsuki","year":"1997","journal-title":"J. Biol. Chem."},{"key":"2026090205152385700_cit9","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1128\/EC.00357-06","article-title":"Molecular cloning\nof apicoplast-targeted Plasmodium falciparum DNA\ngyrase genes: Unique intrinsic ATPase activity and ATP-independent\ndimerization of PfGyrB subunit","volume":"6","author":"Dar","year":"2007","journal-title":"Eukaryotic Cell"},{"key":"2026090205152385700_cit10","unstructured":"www.plasmodb.org (accessed )."},{"key":"2026090205152385700_cit11","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.2174\/0929867023369277","article-title":"Acridine\nderivatives as chemotherapeutic agents","volume":"9","author":"Denny","year":"2002","journal-title":"Curr.\nMed. Chem."},{"key":"2026090205152385700_cit12","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S0022-2836(64)80226-6","article-title":"Heterogeneity\nof the interaction of DNA with acriflavine","volume":"9","author":"Tubbs","year":"1964","journal-title":"J. Mol. Biol."},{"key":"2026090205152385700_cit13","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/nature01097","article-title":"Genome sequence\nof the human malaria parasite Plasmodium falciparum","volume":"419","author":"Gardner","year":"2002","journal-title":"Nature"},{"key":"2026090205152385700_cit14","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1182\/blood-2005-11-026963","article-title":"Transport of the essential nutrient isoleucine in human erythrocytes\ninfected with the malaria parasite Plasmodium falciparum","volume":"109","author":"Martin","year":"2007","journal-title":"Blood"},{"key":"2026090205152385700_cit15","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1124\/mol.104.010553","article-title":"Malaria\nparasites are rapidly killed by dantrolene derivatives specific for\nthe plasmodial surface anion channel","volume":"68","author":"Kang","year":"2005","journal-title":"Mol. Pharmacol."},{"key":"2026090205152385700_cit16","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.cell.2011.05.002","article-title":"Malaria parasite\nclag3 genes determine channel-mediated nutrient uptake by infected\nred blood cells","volume":"145","author":"Nguitragool","year":"2011","journal-title":"Cell"},{"key":"2026090205152385700_cit17","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1124\/mol.112.081224","article-title":"Solute\nrestriction reveals an essential role for clag3-associated channels\nin malaria parasite nutrient acquisition","volume":"82","author":"Pillai","year":"2012","journal-title":"Mol.\nPharmacol."},{"key":"2026090205152385700_cit18","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0166-6851(83)90008-7","article-title":"New permeability\npathways induced in membranes of Plasmodium falciparum infected erythrocytes","volume":"8","author":"Ginsburg","year":"1983","journal-title":"Mol. Biochem. Parasitol."},{"key":"2026090205152385700_cit19","doi-asserted-by":"crossref","first-page":"3339","DOI":"10.1016\/S0021-9258(17)41868-0","article-title":"Transport\nof diverse substrates into malaria-infected erythrocytes via a pathway\nshowing functional characteristics of a chloride channel","volume":"269","author":"Kirk","year":"1994","journal-title":"J. Biol. Chem."},{"key":"2026090205152385700_cit20","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1038\/35023000","article-title":"A voltage-dependent channel involved\nin nutrient uptake by red blood cells infected with the malaria parasite","volume":"406","author":"Desai","year":"2000","journal-title":"Nature"},{"key":"2026090205152385700_cit21","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.ijpara.2006.12.013","article-title":"Electrophysiological studies of malaria parasite-infected\nerythrocytes: Current status","volume":"37","author":"Staines","year":"2007","journal-title":"Int. J. Parasitol."},{"key":"2026090205152385700_cit22","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1128\/EC.00212-06","article-title":"Specific inhibition\nof the plasmodial surface anion channel by dantrolene","volume":"5","author":"Lisk","year":"2006","journal-title":"Eukaryotic Cell"},{"key":"2026090205152385700_cit23","doi-asserted-by":"crossref","first-page":"6396","DOI":"10.1128\/MCB.00719-07","article-title":"Replication in hydroxyurea: It\u2019s a matter of\ntime","volume":"27","author":"Alvino","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"2026090205152385700_cit24","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1111\/j.1365-2958.2008.06316.x","article-title":"Plasmodium falciparum origin recognition complex subunit 5: functional\ncharacterization\nand role in DNA replication foci formation","volume":"69","author":"Gupta","year":"2008","journal-title":"Mol. Microbiol."},{"key":"2026090205152385700_cit25","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1111\/j.1349-7006.2011.02097.x","article-title":"Novel activity of acriflavine against\ncolorectal cancer tumor cells","volume":"102","author":"Hassan","year":"2011","journal-title":"Cancer Sci."},{"key":"2026090205152385700_cit26","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1128\/AAC.40.10.2321","article-title":"Involvement of topoisomerase\nIV and DNA gyrase as ciprofloxacin targets in Streptococcus pneumoniae","volume":"40","author":"Pan","year":"1996","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026090205152385700_cit27","doi-asserted-by":"crossref","first-page":"4474","DOI":"10.1073\/pnas.73.12.4474","article-title":"Novobiocin and coumermycin\ninhibit DNA supercoiling catalyzed by DNA gyrase","volume":"73","author":"Gellert","year":"1976","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026090205152385700_cit28","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/(SICI)1097-0134(199705)28:1<41::AID-PROT4>3.0.CO;2-M","article-title":"The high-resolution\ncrystal structure of a 24-kDa gyrase B fragment from E. coli complexed with one of the most potent coumarin inhibitors, clorobiocin","volume":"28","author":"Tsai","year":"1997","journal-title":"Proteins"},{"key":"2026090205152385700_cit29","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1128\/EC.00149-09","article-title":"A unique 45-amino-acid\nregion in the toprim domain of Plasmodium falciparum gyrase B is essential for its activity","volume":"8","author":"Dar","year":"2009","journal-title":"Eukaryotic\nCell"},{"key":"2026090205152385700_cit30","first-page":"45","article-title":"Drug resistance\nin malaria","volume":"41","author":"Farooq","year":"2004","journal-title":"J.\nVector Borne Dis."},{"key":"2026090205152385700_cit31","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/ng.2624","article-title":"Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia","volume":"45","author":"Miotto","year":"2013","journal-title":"Nat. Genet."},{"key":"2026090205152385700_cit32","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1073\/pnas.49.1.94","article-title":"The structure\nof the DNA-acridine complex","volume":"49","author":"Lerman","year":"1963","journal-title":"Proc. Natl. Acad.\nSci. U.S.A."},{"key":"2026090205152385700_cit33","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/0006-291X(64)90105-6","article-title":"Acriflavine modification of nucleic\nacid formation, mutation induction, and survival in ultraviolet light\nexposed bacteria","volume":"15","author":"Doudney","year":"1964","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2026090205152385700_cit34","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1159\/000257825","article-title":"Zu Pharmakologie des\ntrypaflavins","volume":"66","author":"Bernstein","year":"1933","journal-title":"Dermatalogische Zeitschrift"},{"key":"2026090205152385700_cit35","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/0014-4894(65)90012-3","article-title":"Drug resistance\nin Plasmodium berghei Vincke and Lips, 1948. I. Chloroquine\nresistance","volume":"17","author":"Peters","year":"1965","journal-title":"Exp. Parasitol."}],"container-title":["ACS Chemical Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/cb500476q","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acbcct\/article-pdf\/9\/10\/2366\/15725342\/cb500476q.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acbcct\/article-pdf\/9\/10\/2366\/15725342\/cb500476q.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T09:15:31Z","timestamp":1788340531000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acbcct\/article\/9\/10\/2366\/1479253\/Potent-Antimalarial-Activity-of-Acriflavine-In"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8,4]]},"references-count":35,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2014,8,4]]},"published-print":{"date-parts":[[2014,10,17]]}},"URL":"https:\/\/doi.org\/10.1021\/cb500476q","relation":{},"ISSN":["1554-8929","1554-8937"],"issn-type":[{"value":"1554-8929","type":"print"},{"value":"1554-8937","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8,4]]}}}