title: Synthetic chalcones as potential anti-inflammatory and cancer chemopreventive agents.
abstract: In an effort to develop potent anti-inflammatory and cancer chemopreventive agents, a series of chalcones were prepared by Claisen-Schmidt condensation of appropriate acetophenones with suitable aromatic aldehyde or prepared with appropriate dihydrochalcone reacted with appropriate alkyl bromide or prepared in one-pot procedure involving acetophenone and convenient aromatic aldehyde using ultrasonic agitation on basic alumina. The synthesized products were tested for their inhibitory effects on the activation of mast cells, neutrophils, macrophages, and microglial cells. The potent inhibitors of NO production in macrophages and microglial cells were further evaluated for their in vitro cytotoxic effects against several human cancer cell lines. 2'-Hydroxychalcones 1-3, and 2',5'-dihydroxychalcone 7 exhibited potent inhibitory effects on the release of beta-glucuronidase or lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP)/cytochalasin B (CB). Two 2'-hydroxychalcones (1 and 3) showed potent inhibitory effects on superoxide anion generation in rat neutrophils in response to fMLP/CB. The previously reported chalcone, 5, 6, and 12, exhibited potent inhibitory effect on NO production in lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma)-activated N9 microglial cells or in LPS-activated RAW 264.7 macrophage-like cells. The potent inhibitors 5, 6, and 12 of NO production in macrophages or microglial cells revealed significant or marginal cytotoxic effects against several human cancer lines. Compound 12 manifested potent selective cytotoxicity against human MCF-7 cells and caused cell death by apoptosis. The present results demonstrated that 1-3, and 7 have anti-inflammatory effects and 5, 6, and 12 are potential anti-inflammatory and cancer chemopreventive agents.
authors.affiliation: Department of Microbiology and Immunology, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Shen-Jeu
authors.initials: SJ
authors.lastname: Won
authors.forename: Cheng-Tsung
authors.initials: CT
authors.lastname: Liu
authors.forename: Lo-Ti
authors.initials: LT
authors.lastname: Tsao
authors.forename: Jing-Ru
authors.initials: JR
authors.lastname: Weng
authors.forename: Horng-Huey
authors.initials: HH
authors.lastname: Ko
authors.forename: Jih-Pyang
authors.initials: JP
authors.lastname: Wang
authors.forename: Chun-Nan
authors.initials: CN
authors.lastname: Lin
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D047188:Chalcones / Q000138:chemical synthesis* / Q000494:pharmacology; D018890:Chemoprevention; D006801:Humans; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D016588:Anticarcinogenic Agents; D047188:Chalcones; D008070:Lipopolysaccharides; D009569:Nitric Oxide