Antitumor agents. 271: total synthesis and evaluation of brazilein and analogs as anti-inflammatory and cytotoxic agents.
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.
Yen
Chiao-Ting
CT
Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC 27599 7568, USA.
Nakagawa-Goto
Kyoko
K
Hwang
Tsong-Long
TL
Wu
Pei-Chi
PC
Morris-Natschke
Susan L
SL
Lai
Wan-Chun
WC
Bastow
Kenneth F
KF
Chang
Fang-Rong
FR
Wu
Yang-Chang
YC
Lee
Kuo-Hsiung
KH
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D001578:Benzopyrans; D003603:Cytotoxins; D004365:Drugs, Chinese Herbal; D007192:Indenes; C050295:brazilein