Journal of Medicinal Chemistry p. 4108 - 4112 (1993)
Update date:2022-08-25
Topics:
Cheng
Dong
Liu
Luo
Liu
Chen
Yu
Savaraj
Chou
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.
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