title: Bis-chalcone analogues as potent NO production inhibitors and as cytotoxic agents.
abstract: Chalcones have a distinctive 1,3-diarylpropenone skeleton and exert numerous biological effects. Using a one-step Claisen-Schmidt condensation, we synthesized eleven bis-chalcones (3-13) and three acetyl chalcones (14-16) from substituted aldehydes and diacetylresorcinol. The compounds were tested for in vitro cytotoxic activity against four human cancer cell lines (A549, DU145, KB, and KB-VIN) and inhibition of NO production in lipopolysaccharide (LPS)-activated microglial cells. Among them, four compounds (3, 5, 6, and 13) showed significant cytotoxic activity with EC(50) values ranging from 1.57 to 5.14 μM, and seven compounds (3, 5-8, 10, and 13) displayed potent anti-inflammatory activity by inhibiting NO production with IC(50) values ranging from 0.95 to 8.65 μM. A mechanism of action study of active compounds 6 and 7 discovered that these compounds down-regulated iNOS expression by inhibiting p65 NF-κB activation/nuclear translocation due to prevention of IκBα degradation. Structure-activity relationship (SAR) findings are also discussed.
authors: Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan, ROC.
authors: M
authors: M
authors: Vijaya Bhaskar Reddy
authors: Yuh-Chiang
authors: YC
authors: Shen
authors: Emika
authors: E
authors: Ohkoshi
authors: Kenneth F
authors: KF
authors: Bastow
authors: Keduo
authors: K
authors: Qian
authors: Kuo-Hsiung
authors: KH
authors: Lee
authors: Tian-Shung
authors: TS
authors: Wu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002599:Chalcone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D008070:Lipopolysaccharides; D051996:Transcription Factor RelA; D009569:Nitric Oxide; D002599:Chalcone; D052247:Nitric Oxide Synthase Type II; D019255:NADPH Oxidases; D051550:I-kappa B Kinase