Chemical stability of the peroxide bond enables diversified synthesis of potent tetraoxane antimalarials.
Of 17 prepared 1,2,4,5-tetraoxacyclohexanes stable to reductive and acidic conditions, 3 of them were more active than artemisinin against CQ and MFQ resistant strain TM91C235 and all compounds were more active in vitro against W2 than against D6 strain. In vivo, amines 10 and 11a cured all mice at higher doses with MCD < or = 37.5 (mg/kg)/day. Triol 13 was exceptionally active against melanoma (LOX IMVI) and ovarian cancer (IGROV1), both with LC 50 = 60 nM.
Opsenica
Igor
I
Institute of Chemistry, Technology and Metallurgy, Belgrade, Serbia.
Opsenica
Dejan
D
Smith
Kirsten S
KS
Milhous
Wilbur K
WK
Solaja
Bogdan A
BA
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010545:Peroxides / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D045568:Tetraoxanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000962:Antimalarials; D000970:Antineoplastic Agents; D010545:Peroxides; D045568:Tetraoxanes