| Autor: |
Susan L. Morris-Natschke, Masuo Goto, Xiaoyan Chen, Lan Xie, Kuo Hsiung Lee |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
ACS Med Chem Lett |
| ISSN: |
1948-5875 |
| Popis: |
[Image: see text] Phenanthrene-based tylophorine-1 (PBT-1) was identified previously as a lead compound in an anticancer drug discovery effort based on natural Tylophora alkaloids. An expanded structural optimization using a new more efficient synthetic route provided 14 PBT-derivatives. Eleven compounds displayed obvious antiproliferative activities in cellular assays (GI(50) 0.55–9.32 μM). The most potent compounds 9c, 9g, and 9h (GI(50) < 1 μM) contained a 7-hydroxy group on the phenanthrene B-ring in addition to a pendant piperidine E-ring with different 4-substituents. Compound 9h with NH(2) as the piperidine substituent was at least 4-fold more potent against triple-negative breast cancer MDA-MB-231 than estrogen-responsible breast cancer MCF-7 cell growth. In further biological evaluations, the new active compounds induced cell cycle accumulation in the late S and G2/M phase without interfering with microtubule formation or cell morphology. These results on the optimization of the B- and E-rings of PBT-1 should benefit further development of novel antitumor agents. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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