Synthesis and cytotoxicity of novel 3-aryl-1-(3'-dibenzylaminomethyl-4'-hydroxyphenyl)-propenones and related compounds.
The reaction of various 4'-hydroxychalcones (1a-e) with paraformaldehyde and dibenzylamine led to the formation of a novel series of 4'-hydroxy-3'-dibenzylaminomethyl chalcones (7a-e) instead of 4'-hydroxy-3',5'-bis-(dibenzylaminomethyl)chalcones 4. In order to rationalise the formation of monoadduct 7, energy minimized model structures of 4a and 7a were compared. The in vitro cytotoxic activities of 7a-e were tested against PC-3 cell lines for the first time in this study and compared with the precursor 4'-hydroxychalcones (1a-e). Except for compound 7a (IC(50): 19.85 microM), insertion of dibenzylaminomethyl function into 4'-hydroxychalcones resulted in complete loss of cytotoxic activity. The results suggested that it is not only the pK(a) but also the shape and size of the amine that is critical in governing the cytotoxic activity.
Gul
Halise Inci
HI
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey. incigul1967@yahoo.com
Yerdelen
Kadir Ozden
KO
Das
Umashankar
U
Gul
Mustafa
M
Pandit
Bulbul
B
Li
Pui-Kai
PK
Dimmock
Jonathan Richard
JR
D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis* / Q000494:pharmacology*; D001593:Benzyl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D001665:Binding Sites; D002273:Carcinogens / Q000138:chemical synthesis / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003460:Crystallization; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007659:Ketones / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008352:Mannich Bases; D008958:Models, Molecular; D009153:Mutagens / Q000138:chemical synthesis / Q000494:pharmacology; D011407:Propane / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D018906:Antineoplastic Agents, Alkylating; D001593:Benzyl Compounds; D002273:Carcinogens; D007659:Ketones; D008352:Mannich Bases; D009153:Mutagens; D011407:Propane