title: All trans 1-(3-arylacryloyl)-3,5-bis(pyridin-4-ylmethylene)piperidin-4-ones as curcumin-inspired antineoplastics.
abstract: A series of eleven N-acryloyl/N-cinnamoyl 3,5-bis(pyridin-4-yl)methylene-4-piperidones were synthesized as curcumin-based candidate antineoplastic agents. The cytostatic potency of these compounds was evaluated against three representative cell lines and all compounds were found to exhibit significant anti-cancer cell activity in vitro. QSAR studies using several physicochemical parameters and 50% inhibitory concentration (IC50) values resulted in certain important correlations which will aid design of more potent analogs. Representative test compounds were investigated in the NCI 60-cell line panel where they were found to display a profound cytotoxicity. These compounds were also potent anti-oxidants and inhibitors of human topoisomerase IIα. Representative compounds were well-tolerated by human fibroblasts and by mice during the survival/toxicity studies.
authors.affiliation: Department of Chemistry, Acadia University, Wolfville, Nova Scotia, Canada B4P 2R6.
authors.forename: Nawal K
authors.initials: NK
authors.lastname: Paul
authors.affiliation: Department of Chemistry, Acadia University, Wolfville, Nova Scotia, Canada B4P 2R6.
authors.forename: Mamta
authors.initials: M
authors.lastname: Jha
authors.affiliation: Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, Nova Scotia, Canada B2N 5E3.
authors.forename: Khushwant S
authors.initials: KS
authors.lastname: Bhullar
authors.affiliation: Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, Nova Scotia, Canada B2N 5E3.
authors.forename: H P Vasantha
authors.initials: HP
authors.lastname: Rupasinghe
authors.affiliation: Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.affiliation: Department of Chemistry, Acadia University, Wolfville, Nova Scotia, Canada B4P 2R6. Electronic address: ajha@acadiau.ca.
authors.forename: Amitabh
authors.initials: A
authors.lastname: Jha
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002460:Cell Line; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D066244:Proton Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D010880:Piperidines; D003474:Curcumin
keywords: Anti-oxidant; Curcumin; Cytostatic activity; Michael acceptor; QSAR; Topoisomerase II inhibitors