Antitumor Agents 253. Design, Synthesis, and Antitumor Evaluation of Novel 9-Substituted Phenanthrene-Based Tylophorine Derivatives as Potential Anticancer Agents

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• 作者：Linyi Wei ; Qian Shi ; Kenneth F. Bastow ; Arnold Brossi ; Susan L. Morris-Natschke ; Kyoko Nakagawa-Goto ; Tian-Shung Wu ; Shiow-Lin Pan ; Che-Ming Teng ; Kuo-Hsiung Lee
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：July 26, 2007
• 年：2007
• 卷：50
• 期：15
• 页码：3674 - 3680
• 全文大小：123K
• 年卷期：v.50,no.15(July 26, 2007)
• ISSN：1520-4804

文摘

C9-Substituted phenanthrene-based tylophorine derivatives (PBTs) (13-36) were synthesized and evaluatedas in vitro anticancer agents against the human A549 lung cancer cell line. Twelve active compounds werefurther examined against DU-145 (prostate), ZR-751 (breast), KB (nasopharyngeal), and KB-Vin (multidrugresistant KB subline) human cancer cell lines. They showed potent cytotoxic activity against both wild typeand matched multidrug resistant KB cell lines, and displayed notable selectivity toward DU-145 (prostate)and ZR-751 (breast) cancer cell lines. The mode of action of this class may be distinctly different from thatof other cancer chemotherapeutic compounds. Three PBT analogs were also evaluated in a murine model.Compound 24b showed modest in vivo antitumor activity against human A549 xenograft in nude mice aswell as potent in vitro cytotoxic activity, and thus, is a promising anticancer lead compound.