Antitumor agents 253. Design, synthesis, and antitumor evaluation of novel 9-substituted phenanthrene-based tylophorine derivatives as potential anticancer agents

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

Research output: Contribution to journalArticle

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Abstract

C9-Substituted phenanthrene-based tylophorine derivatives (PBTs) (13-36) were synthesized and evaluated as in vitro anticancer agents against the human A549 lung cancer cell line. Twelve active compounds were further examined against DU-145 (prostate), ZR-751 (breast), KB (nasopharyngeal), and KB-Vin (multidrug resistant KB subline) human cancer cell lines. They showed potent cytotoxic activity against both wild type and 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 that of 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 as well as potent in vitro cytotoxic activity, and thus, is a promising anticancer lead compound.

Original languageEnglish
Pages (from-to)3674-3680
Number of pages7
JournalJournal of Medicinal Chemistry
Volume50
Issue number15
DOIs
Publication statusPublished - Jul 26 2007
Externally publishedYes

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Antineoplastic Agents
Cells
Derivatives
Cell Line
Prostate
Lead compounds
KB Cells
Heterografts
Nude Mice
Human Activities
Lung Neoplasms
Neoplasms
Breast
Breast Neoplasms
tylophorine
phenanthrene
In Vitro Techniques

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Antitumor agents 253. Design, synthesis, and antitumor evaluation of novel 9-substituted phenanthrene-based tylophorine derivatives as potential anticancer agents. / Wei, Linyi; Shi, Qian; Bastow, Kenneth F.; Brossi, Arnold; Morris-Natschke, Susan L.; Nakagawa-Goto, Kyoko; Wu, Tian Shung; Pan, Shiow Lin; Teng, Che Ming; Lee, Kuo Hsiung.

In: Journal of Medicinal Chemistry, Vol. 50, No. 15, 26.07.2007, p. 3674-3680.

Research output: Contribution to journalArticle

Wei, Linyi ; Shi, Qian ; Bastow, Kenneth F. ; Brossi, Arnold ; Morris-Natschke, Susan L. ; Nakagawa-Goto, Kyoko ; Wu, Tian Shung ; Pan, Shiow Lin ; Teng, Che Ming ; Lee, Kuo Hsiung. / Antitumor agents 253. Design, synthesis, and antitumor evaluation of novel 9-substituted phenanthrene-based tylophorine derivatives as potential anticancer agents. In: Journal of Medicinal Chemistry. 2007 ; Vol. 50, No. 15. pp. 3674-3680.
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AU - Morris-Natschke, Susan L.

AU - Nakagawa-Goto, Kyoko

AU - Wu, Tian Shung

AU - Pan, Shiow Lin

AU - Teng, Che Ming

AU - Lee, Kuo Hsiung

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