title: Comparison of hematin-targeting properties of pynacrine, an acridine analog of the benzonaphthyridine antimalarial pyronaridine.
abstract: The hematin-targeting properties of pynacrine, an acridine analog of the schizontocidal antimalarial drug, pyronaridine, were evaluated to probe the role of the latter's benzonaphthyridine moiety. Pynacrine was as active as pyronaridine in inhibiting glutathione-induced hematin degradation and in enhancing hematin-mediated membrane lysis. It formed a 1:2 complex with hematin but was 50-fold less effective in inhibiting β-hematin formation. However, pynacrine was as potent as pyronaridine in inhibiting intra-erythrocytic Plasmodium falciparum growth in culture, suggesting that it has other off-target(s) effects.
authors.affiliation: Division of Toxicology, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Narumon
authors.initials: N
authors.lastname: Sereekhajornjaru
authors.affiliation: Division of Toxicology, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Chanat
authors.initials: C
authors.lastname: Somboon
authors.affiliation: National Centre for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Klong Luang, Pathumthani 12120, Thailand.
authors.forename: Roonglawan
authors.initials: R
authors.lastname: Rattanajak
authors.affiliation: Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: William A
authors.initials: WA
authors.lastname: Denny
authors.affiliation: Department of Chemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Prapin
authors.initials: P
authors.lastname: Wilairat
authors.affiliation: Division of Toxicology, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand. Electronic address: saranya.aup@mahidol.ac.th.
authors.forename: Saranya
authors.initials: S
authors.lastname: Auparakkitanon
mesh_terms: D000166:Acridines / Q000494:pharmacology*; D000962:Antimalarials / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects; D006420:Hemeproteins / Q000037:antagonists & inhibitors; D006801:Humans; D008288:Malaria / Q000188:drug therapy; D009287:Naphthyridines / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects*
chemical_list: D000166:Acridines; D000962:Antimalarials; D006420:Hemeproteins; D009287:Naphthyridines; C000602282:pynacrine; C027871:pyronaridine
keywords: 9-Aminoacridine; Antiplasmodial; Hematin; Plasmodium falciparum; Pynacrine; Pyronaridine