3-(3,4,5-Trimethoxyphenyl)-1-oxo-2-propene: a novel pharmacophore displaying potent multidrug resistance reversal and selective cytotoxicity.
This study revealed that various alicyclic and acyclic compounds containing the 3-(3,4,5-trimethoxyphenyl)-2-propenoyl group displayed potent MDR reversal properties. In particular, a concentration of 4 microg/ml of 2,5-bis(3,4,5-trimethoxyphenylmethylene)cyclopentanone was 31 times more potent than verapamil as a MDR revertant. In general, they were selectively toxic to malignant rather than normal cells. Two representative compounds induced apoptosis in human HL-60 cells and markedly activated caspase-3.
Das
Umashankar
U
College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, Canada SK S7N 5C9.
Kawase
Masami
M
Sakagami
Hiroshi
H
Ideo
Atsushi
A
Shimada
Jun
J
Molnár
Joseph
J
Baráth
Zoltán
Z
Bata
Zsuzsanna
Z
Dimmock
Jonathan R
JR
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011407:Propane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013050:Spectrometry, Fluorescence
C520655:3-(3,4,5-trimethoxyphenyl)-1-oxo-2-propene; D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D020169:Caspases; D011407:Propane