Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antineoplastic Agents / chemical synthesis*
-
Antineoplastic Agents / pharmacology
-
Cell Division / drug effects
-
Chalcone / analogs & derivatives*
-
Chalcone / chemical synthesis
-
Chalcone / pharmacology
-
Drug Design
-
Drug Screening Assays, Antitumor
-
Enzyme Inhibitors / chemical synthesis
-
Enzyme Inhibitors / pharmacology
-
Humans
-
Hydrocarbons, Fluorinated / chemical synthesis
-
Hydrocarbons, Fluorinated / pharmacology
-
Inhibitory Concentration 50
-
Lipid Peroxidation / drug effects
-
Lipoxygenase Inhibitors*
-
Male
-
Microsomes, Liver / enzymology
-
Organ Specificity
-
Rats
-
Rats, Wistar
-
Tumor Cells, Cultured
Substances
-
Antineoplastic Agents
-
Enzyme Inhibitors
-
Hydrocarbons, Fluorinated
-
Lipoxygenase Inhibitors
-
Chalcone