TY - JOUR
T1 - Design of Antineoplastic Agents on the Basis of the “2-Phenylnaphthalene-Type” Structural Pattern. 2. Synthesis and Biological Activity Studies of Benzo[A]naphtho[2,3-d]furan-6,11-dione Derivatives
AU - Cheng, C. C.
AU - Dong, Qing
AU - Liu, Dun Fu
AU - Luo, Yi Lin
AU - Liu, Leroy F.
AU - Chen, Allan Y.
AU - Yu, Chiang
AU - Savaraj, Niramol
AU - Chou, Ting Chao
PY - 1993
Y1 - 1993
N2 - 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.
AB - 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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U2 - 10.1021/jm00077a016
DO - 10.1021/jm00077a016
M3 - Article
C2 - 8258835
AN - SCOPUS:0027741337
SN - 0022-2623
VL - 36
SP - 4108
EP - 4112
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 25
ER -