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

Based on the ''2-phenylnaphthalene-type'' structural pattern hypothesi s developed in our laboratory, a number of benzo [b] naphtho[2,3-d] fu ran-6,11-diones were designed, synthesized, and evaluated in vitro for their inhibitory action against the growth of human promyelocytic leu kemia cells (HL-GO),small-cell lung cancer (SCLC), SCLC cells resistan t to cisplatin (SCLC/CDDP), National Cancer Institute's disease-orient ed primary antitumor 60 cell-line panel, and drug-stimulated topoisome rase II-mediated DNA cleavages. Many compounds designed were found to possess potent activity in one or more of the biological tests. In gen eral, activity found in one of the cell lines tested is often echoed i n other cell lines and many also expressed substantial inhibitory acti vity against topoisomerase II-mediated cleavage activities. One of the se compounds, y]-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 hypo thesis has received substantial support through experimental verificat ion.