Abstract |
In our exploration of new biologically active chemical entities, we designed and synthesized a novel class of antitumor agents, substituted 4-amino-7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-one (ATBO) analogs. We evaluated their cytotoxic activity against seven human tumor cell lines from different tissues, and established preliminary structure-activity relationships (SAR). All analogs, except 8, 9, and 25-27, displayed potent tumor cell growth inhibitory activity. Especially, compounds 15 and 33 with a 4-methoxyphenyl group at position C-4 were extremely potent with ED(50) values of 0.008-0.064 and 0.035-0.32 μM, respectively. Compound 15 was the most potent analog compared with structurally related neo-tanshinlactone (e.g., 1) and 4-amino-2H-benzo[h]chromen-2-one (ABO, e.g., 4) analogs, and thus merits further exploration as an anti- cancer drug candidate.
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Authors | Yizhou Dong, Kyoko Nakagawa-Goto, Chin-Yu Lai, Susan L Morris-Natschke, Kenneth F Bastow, Kuo-Hsiung Lee |
Journal | Bioorganic & medicinal chemistry letters
(Bioorg Med Chem Lett)
Vol. 21
Issue 1
Pg. 546-9
(Jan 01 2011)
ISSN: 1464-3405 [Electronic] England |
PMID | 21087859
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 2010 Elsevier Ltd. All rights reserved. |
Chemical References |
- 4-((4'-methoxyphenyl)amino)-7,8,9,10-tetrahydro-2H-benzo(h)chromen-2-one
- Aniline Compounds
- Antineoplastic Agents
- Chromones
- Coumarins
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Topics |
- Aniline Compounds
(chemical synthesis, chemistry, therapeutic use)
- Antineoplastic Agents
(chemical synthesis, chemistry, therapeutic use)
- Cell Line, Tumor
- Chromones
(chemical synthesis, chemistry, therapeutic use)
- Coumarins
(chemical synthesis, chemistry, therapeutic use)
- Drug Design
- Drug Screening Assays, Antitumor
- Humans
- Neoplasms
(drug therapy)
- Structure-Activity Relationship
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