Antitumor agents. 271: Total synthesis and evaluation of brazilein and analogs as anti-inflammatory and cytotoxic agents

• Published in: Bioorganic & medicinal chemistry letters Vol. 20; no. 3; pp. 1037 - 1039
• Main Authors: Yen, Chiao-Ting, Nakagawa-Goto, Kyoko, Hwang, Tsong-Long, Wu, Pei-Chi, Morris-Natschke, Susan L., Lai, Wan-Chun, Bastow, Kenneth F., Chang, Fang-Rong, Wu, Yang-Chang, Lee, Kuo-Hsiung
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.02.2010; Elsevier
• Subjects: Anti-inflammatory; Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis; Anti-Inflammatory Agents, Non-Steroidal - isolation & purification; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Benzopyrans; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Brazilein; Cell Line, Tumor; Cytotoxic; Cytotoxins - chemical synthesis; Cytotoxins - isolation & purification; Cytotoxins - pharmacology; Drug Evaluation, Preclinical - methods; Drugs, Chinese Herbal - chemical synthesis; Drugs, Chinese Herbal - isolation & purification; Drugs, Chinese Herbal - pharmacology; General aspects; Homoisoflavonoid; Humans; Indenes; Medical sciences; Neutrophils - drug effects; Neutrophils - immunology; Pharmacology. Drug treatments; Homoisoflavonoid; Cytotoxic; Anti-inflammatory; Brazilein; Antineoplastic agent; Human; Lung; Antiinflammatory agent; Cytotoxicity; Epidermis; Flavonoid; In vitro; Biological activity; Total synthesis; Cell line; KB cell line; Phenols; Acylate; Prostate; Tumor cell
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2009.12.041

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 μM, 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 μM against the four tested cancer cell lines.