Synthesis and biological activities of fluorinated chalcone derivatives.
We have designed and synthesized new 5-lipoxygenase inhibitors, fluorinated 3,4-dihydroxychalcones, and evaluated their biological activities with respect to antiperoxidation activity and in vitro antitumor activities. All fluorinated chalcones tested showed 5-lipoxygenase inhibition on rat basophilic leukemia-1 (RBL-1) cells and inhibitory action on Fe(3+)-ADP induced NADPH-dependent lipid peroxidation in rat liver microsomes. The potencies were comparable or better to that of the lead 3,4-dihydroxychalcone. 6-Fluoro-3,4-dihydroxy-2',4'-dimethoxy chalcone (7) was the most effective compound in the in vitro assay using a human cancer cell line panel (HCC panel) consisting of 39 systems.
Nakamura
Chika
C
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770-8514, Japan.
Kawasaki
Nobuhide
N
Miyataka
Hideki
H
Jayachandran
Ezhuthachan
E
Kim
In Ho
IH
Kirk
Kenneth L
KL
Taguchi
Takeo
T
Takeuchi
Yoshio
Y
Hori
Hitoshi
H
Satoh
Toshio
T
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D015227:Lipid Peroxidation / Q000187:drug effects; D016859:Lipoxygenase Inhibitors; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009928:Organ Specificity; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D006845:Hydrocarbons, Fluorinated; D016859:Lipoxygenase Inhibitors; D002599:Chalcone