Antitumor agents 281. Design, synthesis, and biological activity of substituted 4-amino-7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-one analogs (ATBO) as potent in vitro anticancer agents

作者：Dong Yizhou; Nakagawa Goto Kyoko; Lai Chin Yu; Morris Natschke Susan L; Bastow Kenneth F; Lee Kuo Hsiung^*

来源：Bioorganic & Medicinal Chemistry Letters, 2011, 21(1): 546-549.

DOI：10.1016/j.bmcl.2010.10.074

• 4-Amino-7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-ones(ATBO)
• Cytotoxic activity
• Neo-tanshinlactone

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 mu M, 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.

• 出版日期2011-1
• 单位中国医科大学