Synthesis of cytotoxic fluorinated quassinoids.
The C-15 senecioyl side chain of brusatol was interchanged with fluorinated acyl groups, and the C-3 hydroxy group of bruceolide was esterified with fluorinated acyl chlorides. These fluorinated quassinoids 11, 12, 13, and 17 showed significant cytotoxic activity against eight human cancer cell lines including small and non-small cell lung, colon, CNS, ovarian and renal cancers, leukemia, and melanoma with 17 being about 100 times more potent than 11, 12, and 13. The activity of 17 was similar to that of bruceantin (1) in this in vitro cell line panel.
Ohno
N
N
Interdisciplinary Studies of Natural Environment, Faculty of Integrated Arts and Sciences, Hiroshima University, Japan.
Fukamiya
N
N
Okano
M
M
Tagahara
K
K
Lee
K H
KH
D000215:Acylation; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005461:Fluorine; D005900:Glaucarubin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008956:Models, Chemical; D036702:Quassins; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D036702:Quassins; C020237:brusatol; D005461:Fluorine; D005900:Glaucarubin; C002550:bruceantin