title: Antimalarial activity of 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251) and its carboxylic acid derivatives.
abstract: Malaria is one of the world's deadliest diseases and is becoming an increasingly serious problem as malaria parasites develop resistance to most of the antimalarial drugs used today. We previously reported the in vitro and in vivo antimalarial potencies of 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) and 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251) against Plasmodium falciparum and Plasmodium berghei parasites. To improve water-solubility for synthetic peroxides, a variety of cyclic peroxides having carboxyl functionality was prepared based on the antimalarial candidate, N-251, and their antimalarial activities were determined. The reactions of N-89 and its derivatives with Fe(II) demonstrated a highly efficient formation of the corresponding carbon radical which may be suspected as a key for the antiparasitic activity.
authors.affiliation: Faculty of Pharmaceutical Sciences, Okayama University, Kita-ku, Okayama, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sato
authors.forename: Satoru
authors.initials: S
authors.lastname: Kawai
authors.forename: Akiko
authors.initials: A
authors.lastname: Hiramoto
authors.forename: Masayuki
authors.initials: M
authors.lastname: Morita
authors.forename: Natsuki
authors.initials: N
authors.lastname: Tanigawa
authors.forename: Yukari
authors.initials: Y
authors.lastname: Nakase
authors.forename: Yuka
authors.initials: Y
authors.lastname: Komichi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Osamu
authors.initials: O
authors.lastname: Hiraoka
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hiramoto
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Tokuhara
authors.forename: Araki
authors.initials: A
authors.lastname: Masuyama
authors.forename: Masatomo
authors.initials: M
authors.lastname: Nojima
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Higaki
authors.forename: Hikoya
authors.initials: H
authors.lastname: Hayatsu
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Wataya
authors.forename: Hye-Sook
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000627:therapeutic use; D002244:Carbon / Q000737:chemistry / Q000378:metabolism; D002264:Carboxylic Acids / Q000737:chemistry; D004353:Drug Evaluation, Preclinical; D005296:Ferrous Compounds / Q000378:metabolism; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D000441:Hexanols / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000627:therapeutic use; D006801:Humans; D020128:Inhibitory Concentration 50; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D008813:Mice, Inbred ICR; D010084:Oxidation-Reduction; D010545:Peroxides / Q000737:chemistry / Q000378:metabolism; D010962:Plasmodium berghei / Q000187:drug effects* / Q000254:growth & development; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D013141:Spiro Compounds / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000627:therapeutic use; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D002264:Carboxylic Acids; D005296:Ferrous Compounds; D005609:Free Radicals; D000441:Hexanols; D010545:Peroxides; D013141:Spiro Compounds; D002244:Carbon