title: 1,3-diaryl-2-propenones and 2-benzylidene-1,3-indandiones: a quest for compounds displaying greater toxicity to neoplasms than normal cells.
abstract: A series of 1,3-diaryl-2-propenones 2a-j and analogous 2-benzylidene-1,3-indandiones 3a-j were evaluated against various neoplasms and normal cells. In general, greater cytotoxic potencies and selective toxicity to human malignant cells were observed by the compounds in series 2 rather than 3. In particular, 2i emerged as a lead molecule having an average CC(50) figure of 8.6 µM and a selective index value of 18. Various physicochemical features of 2a-j were correlated with the cytotoxic potencies to neoplastic cell lines which provide guidelines for expansion of this series of compounds. The enone 2i induced internucleosomal DNA fragmentation and activated caspase-3 in HL-60 cells suggesting that one of the ways in which the cytotoxicity of the compounds in series 2 is mediated towards some of the cell lines used in this study is by apoptosis. Neurotoxicity in mice was generally lower in series 2 than 3a-j.
authors.affiliation: Drug Design and Discovery Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Hari N
authors.initials: HN
authors.lastname: Pati
authors.forename: Umashankar
authors.initials: U
authors.lastname: Das
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakagami
authors.forename: Masame
authors.initials: M
authors.lastname: Kawase
authors.forename: Qing
authors.initials: Q
authors.lastname: Chu
authors.forename: Qintao
authors.initials: Q
authors.lastname: Wang
authors.forename: James P
authors.initials: JP
authors.lastname: Stables
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Dimmock
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D053938:DNA Fragmentation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007189:Indans / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000209:etiology; D021281:Quantitative Structure-Activity Relationship; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D007189:Indans; D053148:Caspase 3
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