Laboratory of Microbial Chemistry, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu, Shiga 525-8577, Japan.
Bioorg Med Chem Lett. 2010 Feb 15;20(4):1330-3. doi: 10.1016/j.bmcl.2010.01.016. Epub 2010 Jan 11.
In previous work, botryllamides discovered from the marine ascidian Botryllus tyreus were characterized as selective inhibitors of the ABCG2 multidrug transporter. However, the structural basis for this activity could not be established. In this study, botryllamide F, the core botryllamide structure, and botryllamide G, the most potent botryllamide ABCG2 inhibitor, were synthesized along with a series of structural variants for evaluation of structure-activity relationships. The biological activity of synthetic botryllamide analogs implied that the 2-methoxy-p-coumaric acid portion, and the degree of double bond conjugation within this group, were critical for inhibition of ABCG2. However, variations in the substituents on the two aryl groups did not appear to significantly impact the potency or degree of inhibition.
在之前的工作中，从海洋被囊动物泡叶藻属中发现的 botryllamides 被鉴定为 ABCG2 多药转运蛋白的选择性抑制剂。然而，这种活性的结构基础尚无法确定。在这项研究中，botryllamide F（botryllamide 的核心结构）和 botryllamide G（最有效的 botryllamide ABCG2 抑制剂）以及一系列结构变体被合成，以评估结构-活性关系。合成 botryllamide 类似物的生物学活性表明，2-甲氧基对香豆酸部分以及该基团内双键的共轭程度对于抑制 ABCG2 至关重要。然而，两个芳基上取代基的变化似乎并没有显著影响抑制的效力或程度。
