Antitumor effects of curcumin and structurally beta-diketone modified analogs on multidrug resistant cancer cells.
Using concepts of bioisostery a series of curcumin analogs were synthesized: the diketonic system of the compound was elaborated into enaminones, oximes, and the isoxazole heterocycle. The cell growth inhibitory and apoptosis inducing effects of the new analogs were evaluated by in vitro assays in the hepatocellular carcinoma HA22T/VGH cells, as well as in the MCF-7 breast cancer cell line and in its multidrug resistant (MDR) variant MCF-7R. Increased antitumor activity on all cell lines was found with the isoxazole analog and especially with the benzyl oxime derivative; in the HA22T/VGH cell model, the latter compound inhibited constitutive NF-kappaB activation.
Simoni
Daniele
D
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Via Fossato di Mortara 17/19, 44100 Ferrara, Italy. smd@unife.it
Rizzi
Michele
M
Rondanin
Riccardo
R
Baruchello
Riccardo
R
Marchetti
Paolo
P
Invidiata
Francesco Paolo
FP
Labbozzetta
Manuela
M
Poma
Paola
P
Carina
Valeria
V
Notarbartolo
Monica
M
Alaimo
Alessandra
A
D'Alessandro
Natale
N
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D003474:Curcumin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007659:Ketones / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization
D000970:Antineoplastic Agents; D007659:Ketones; D003474:Curcumin