title: Potent antimalarial activity of acriflavine in vitro and in vivo.
abstract: 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.
authors.affiliation: Special Centre for Molecular Medicine, Jawaharlal Nehru University , New Delhi 110067, India.
authors.forename: Srikanta
authors.initials: S
authors.lastname: Dana
authors.forename: Dhaneswar
authors.initials: D
authors.lastname: Prusty
authors.forename: Devender
authors.initials: D
authors.lastname: Dhayal
authors.forename: Mohit Kumar
authors.initials: MK
authors.lastname: Gupta
authors.forename: Ashraf
authors.initials: A
authors.lastname: Dar
authors.forename: Sobhan
authors.initials: S
authors.lastname: Sen
authors.forename: Pritam
authors.initials: P
authors.lastname: Mukhopadhyay
authors.forename: Tridibesh
authors.initials: T
authors.lastname: Adak
authors.forename: Suman Kumar
authors.initials: SK
authors.lastname: Dhar
mesh_terms: D000167:Acriflavine / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects* / Q000469:parasitology; D006801:Humans; D066298:In Vitro Techniques; D007364:Intercalating Agents / Q000494:pharmacology; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects*; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D007364:Intercalating Agents; D059005:Topoisomerase II Inhibitors; D000167:Acriflavine
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