Antimalarial, Antiproliferative, and Antitumor Activities of Artemisinin-Derived, Chemically Robust, Trioxane Dimers

• Published in: Journal of medicinal chemistry Vol. 42; no. 21; pp. 4275 - 4280
• Main Authors: Posner, Gary H, Ploypradith, Poonsakdi, Parker, Michael H, O'Dowd, Hardwin, Woo, Soon-Hyung, Northrop, John, Krasavin, Mikhail, Dolan, Patrick, Kensler, Thomas W, Xie, Suji, Shapiro, Theresa A
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 21.10.1999; Amer Chemical Soc
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimalarials - chemical synthesis; Antimalarials - chemistry; Antimalarials - pharmacology; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antiparasitic agents; Artemisinins; Biological and medical sciences; Cells, Cultured; Chemistry, Medicinal; Drug Screening Assays, Antitumor; General aspects; Humans; Inhibitory Concentration 50; Lactones - chemical synthesis; Lactones - chemistry; Lactones - pharmacology; Life Sciences & Biomedicine; Medical sciences; Mice; Neoplasm Transplantation; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Plasmodium falciparum - drug effects; Science & Technology; Sesquiterpenes - chemical synthesis; Sesquiterpenes - chemistry; Sesquiterpenes - pharmacology; Structure-Activity Relationship; IN-VITRO; ACID; CONVERSION; ANALOGS; DERIVATIVES; CYTOTOXICITY; Antineoplastic agent; Endoperoxide; Antimalarial; Antipsoriatic agent; Cytotoxicity; Oxygen heterocycle; Antiprotozoal agent; Peracetal; Plasmodium falciparum; Structure activity relation; Parasiticid; Keratinocyte; Chemical synthesis; Tumor cell; Human; Protozoa; Apicomplexa; Rodentia; Benzene derivatives; Tetracyclic compound; In vitro; Vertebrata; Mammalia; Cell line; Mouse; Animal; Dimer; Organic peroxide
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm990363d

Nine C-10 non-acetal derivatives of the natural trioxane artemisinin (1) were prepared as dimers using some novel chemistry. As designed, each dimer was stable chemically. C-10 Olefinic dimers 7 and C-10 saturated dimers 8 − 13 all showed good to excellent antimalarial and antiproliferative activities in vitro. Dimers 8, 10, and 12 were especially potent and selective at inhibiting growth of some human cancer cell lines in the NCI in vitro 60-cell line assay.