title: Antimalarial activity of endoperoxide compound 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol.
abstract: Plasmodium falciparum, the major causative parasite for the disease, has acquired resistance to most of the antimalarial drugs used today, presenting an immediate need for new antimalarial drugs. Here, we report the in vitro and in vivo antimalarial activities of 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251) against P. falciparum and Plasmodium berghei parasites. The N-251 showed high antimalarial potencies both in the in vitro and the in vivo tests (EC(50) 2.3×10(-8) M; ED(50) 15 mg/kg (per oral)). The potencies were similar to that of artemisinin in vitro and greater than artemisinin's activity in vivo (p.o.). In addition, N-251 has little toxicity: a single oral administration at 2000 mg/kg to a rat gave no health problems to it. Administration of N-251 to mice bearing 1% of parasitemia (per oral 68 mg/kg, 3 times a day for 3 consecutive days) resulted in a dramatic decrease in the parasitemia: all the 5 mice given N-251 were cured without any recurrence, with no diarrhea or weight loss occurring in the 60 days of experiment. N-251 deserves more extensive clinical evaluation, desirably including future trials in the human.
authors.affiliation: Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sato
authors.forename: Akiko
authors.initials: A
authors.lastname: Hiramoto
authors.forename: Masayuki
authors.initials: M
authors.lastname: Morita
authors.forename: Masahiro
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Yuka
authors.initials: Y
authors.lastname: Komich
authors.forename: Yukari
authors.initials: Y
authors.lastname: Nakase
authors.forename: Natsuki
authors.initials: N
authors.lastname: Tanigawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Hiraoka
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hiramoto
authors.forename: Hikoya
authors.initials: H
authors.lastname: Hayatsu
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Higaki
authors.forename: Satoru
authors.initials: S
authors.lastname: Kawai
authors.forename: Araki
authors.initials: A
authors.lastname: Masuyama
authors.forename: Masatomo
authors.initials: M
authors.lastname: Nojima
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Wataya
authors.forename: Hye-Sook
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D037621:Artemisinins / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004359:Drug Therapy, Combination; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D006574:Heterocyclic Compounds, 2-Ring / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D000441:Hexanols / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D018512:Parasitemia / Q000188:drug therapy; D021261:Parasitic Sensitivity Tests; D010962:Plasmodium berghei / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects*; D051381:Rats; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D016019:Survival Analysis; D045568:Tetraoxanes
chemical_list: C430901:1,2,6,7-tetraoxaspiro(7.11)nonadecane; C571809:6-(1,2,6,7-tetraoxaspiro(7.11)nonadec-4-yl)hexan-1-ol; D000962:Antimalarials; D037621:Artemisinins; D006574:Heterocyclic Compounds, 2-Ring; D000441:Hexanols; D013141:Spiro Compounds; D045568:Tetraoxanes; C031327:artemisinin