title: Synthesis and cytotoxicity of novel 3-aryl-1-(3'-dibenzylaminomethyl-4'-hydroxyphenyl)-propenones and related compounds.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey. incigul1967@yahoo.com
authors.forename: Halise Inci
authors.initials: HI
authors.lastname: Gul
authors.forename: Kadir Ozden
authors.initials: KO
authors.lastname: Yerdelen
authors.forename: Umashankar
authors.initials: U
authors.lastname: Das
authors.forename: Mustafa
authors.initials: M
authors.lastname: Gul
authors.forename: Bulbul
authors.initials: B
authors.lastname: Pandit
authors.forename: Pui-Kai
authors.initials: PK
authors.lastname: Li
authors.forename: Jonathan Richard
authors.initials: JR
authors.lastname: Dimmock
mesh_terms: 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
chemical_list: D018906:Antineoplastic Agents, Alkylating; D001593:Benzyl Compounds; D002273:Carcinogens; D007659:Ketones; D008352:Mannich Bases; D009153:Mutagens; D011407:Propane