Syntheses and cytotoxic properties of the curcumin analogs 2,6-bis(benzylidene)-4-phenylcyclohexanones.
Fifteen curcumin analogs were synthesized and tested for in-vitro cytotoxicity towards B16 and L1210 murine cancer cell lines using an MTT assay. Significant activity was discovered for two analogs: 8 (B16 IC(50) = 1.6 microM; L1210 IC(50) = 0.35 microM) and 9 (B16 IC(50) = 0.51 microM; L1210 IC(50 )= 1.2 microM). Several other analogs exhibited notable cytotoxicity. The data from quantitative structure-activity relationships suggest that large electron-withdrawing substituents placed in the meta-position of the arylidene aryl rings enhance potencies. Compounds 8 and 9 were found using a cell-based assay to have virtually no effects on microtubules at concentrations up to 40 microM. These results suggest that tubulin inhibition is not the principal mechanism by which the curcumin analogs act.
Department of Chemistry, Hope College, Holland, MI 49423, USA.
Ryan
R
Davis
Umashankar
U
Das
Hilary
H
Mackay
Toni
T
Brown
Susan L
SL
Mooberry
Jonathan R
JR
Dimmock
Moses
M
Lee
Hari
H
Pati
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D003474:Curcumin / Q000031:analogs & derivatives*; D003512:Cyclohexanones / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D020128:Inhibitory Concentration 50; D051379:Mice; D008870:Microtubules / Q000187:drug effects; D021281:Quantitative Structure-Activity Relationship; D014404:Tubulin / Q000187:drug effects
D000970:Antineoplastic Agents; D003512:Cyclohexanones; D014404:Tubulin; D003474:Curcumin