Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7568, USA.
Bioorg Med Chem Lett. 2011 Jan 1;21(1):546-9. doi: 10.1016/j.bmcl.2010.10.074. Epub 2010 Nov 17.
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.
在探索新的具有生物活性的化学实体的过程中，我们设计并合成了一类新型的抗肿瘤剂，取代了 4-氨基-7,8,9,10-四氢-2H-苯并[h]色烯-2-酮（ATBO）类似物。我们评估了它们对七种来自不同组织的人肿瘤细胞系的细胞毒性活性，并建立了初步的构效关系（SAR）。除了 8、9 和 25-27 之外，所有类似物都显示出很强的肿瘤细胞生长抑制活性。特别是，在 C-4 位带有 4-甲氧基苯基的化合物 15 和 33 具有极强的活性，ED(50)值分别为 0.008-0.064 和 0.035-0.32 μM。与结构相关的 neo-tanshinlactone（例如 1）和 4-氨基-2H-苯并[h]色烯-2-酮（ABO，例如 4）类似物相比，化合物 15 是最有效的类似物，因此值得进一步探索作为抗癌药物候选物。
