title: Antitumor agents. 271: total synthesis and evaluation of brazilein and analogs as anti-inflammatory and cytotoxic agents.
abstract: The first total synthesis of the naturally occurring tetracyclic homoisoflavonoid brazilein (1) and 14 new analogs (1a-n) is reported. Target compounds and intermediates were assayed for anti-inflammatory effects on superoxide anion generation and elastase release by human neutrophils in response to fMLP/CB, and for cytotoxic activity against nasopharyngeal (KB), vincristine-resistant nasopharyngeal (KBvin), lung (A549) and prostate (DU-145) human cancer cell lines. The most active compound 1b showed potent effects on superoxide anion generation and elastase release with IC(50) values of 1.2 and 1.9 microM, respectively, and was 65 times more potent than phenylmethylsulfonyl fluoride (PMSF), the positive control, in the latter assay. Additionally, 1b exhibited broad spectrum in vitro anticancer activity with IC(50) values of 6-11 microM against the four tested cancer cell lines.
authors.affiliation: Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC 27599 7568, USA.
authors.forename: Chiao-Ting
authors.initials: CT
authors.lastname: Yen
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nakagawa-Goto
authors.forename: Tsong-Long
authors.initials: TL
authors.lastname: Hwang
authors.forename: Pei-Chi
authors.initials: PC
authors.lastname: Wu
authors.forename: Susan L
authors.initials: SL
authors.lastname: Morris-Natschke
authors.forename: Wan-Chun
authors.initials: WC
authors.lastname: Lai
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Bastow
authors.forename: Fang-Rong
authors.initials: FR
authors.lastname: Chang
authors.forename: Yang-Chang
authors.initials: YC
authors.lastname: Wu
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology; D001578:Benzopyrans; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D007192:Indenes; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D001578:Benzopyrans; D003603:Cytotoxins; D004365:Drugs, Chinese Herbal; D007192:Indenes; C050295:brazilein