- Design of antineoplastic agents on the basis of the '2-phenylnaphthalene- type' structural pattern. 2. Synthesis and biological activity studies of benzo[b]naphtho[2,3-d]furan-6,11-dione derivatives
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Based on the '2-phenylnaphthalene-type' structural pattern hypothesis developed in our laboratory, a number of benzo[b]naphtho[2,3-d]furan-6,11- diones were designed, synthesized, and evaluated in vitro for their inhibitory action against the growth of human promyelocytic leukemia cells (HL-60), small-cell lung cancer (SCLC), SCLC cells resistant to cisplatin (SCLC/CDDP), National Cancer Institute's disease-oriented primary antitumor 60 cell-line panel, and drug-stimulated topoisomerase II-mediated DNA cleavages. Many compounds designed were found to possess potent activity in one or more of the biological tests. In general, activity found in one of the cell lines tested is often echoed in other cell lines and many also expressed substantial inhibitory activity against topoisomerase II-mediated cleavage activities. One of these compounds, 3-[2-(dimethylamino)ethoxy]-1- hydroxybenzo[b]naphtho[2,3-d]furan-6,11-dione (8j), exhibited strong inhibitory activity throughout the entire series of test panel. Thus, it appears that the proposed structural pattern hypothesis has received substantial support through experimental verification.
- Cheng,Dong,Liu,Luo,Liu,Chen,Yu,Savaraj,Chou
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- Synthesis, cytotoxicity and topoisomerase II inhibitory activity of benzonaphthofurandiones
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Benzonaphthofurandiones containing four coplanar fused aromatic rings were synthesized and evaluated for their cytotoxicity against five human cancer cell lines, and their inhibitory activity on topoisomerases. These benzonaphthofurandiones were prepared by condensation of 2,3- dichloronaphthoquinone and three aromatic diols with base catalysts in alcohol. The synthesized compounds were o-alkylated with six dialkylaminoalkyl halides. The hydroxy derivatives (8a-8g) exhibited relatively potent cytotoxicity among the prepared compounds. These compounds were evaluated as excellent inhibitors against topoisomerase II (topo II). Especially, the hydroxy analogue with branched methyl side chain (8e) showed high cytotoxicity against cancer cell lines and good inhibitory activity on topo II.
- Rhee, Hee-Kyung,Kwon, Youngjoo,Chung, Hwa-Jin,Lee, Sang Kook,Choo, Hea-Young Park
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p. 2391 - 2396
(2012/06/01)
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