Foundation for Research in Life Sciences c/o Insubrias Park, Via Roberto Lepetit 34, 21040 Gerenzano, Italy.
Bioorg Chem. 2011 Aug;39(4):151-8. doi: 10.1016/j.bioorg.2011.07.003. Epub 2011 Jul 27.
6[3-(1-Adamantyl)-4-methoxyphenyl]-2-naphthoic acid (Adapalene®), a synthetic aromatic retinoid specific for RARβ and RARγ receptors, has been prepared utilizing a Pd/C-mediated Suzuki coupling between 6-bromo-2-naphthoic acid and 4-methoxyphenyl boronic acid, followed by introduction of an adamantyl group in the position 3 of the formed 6-(4-methoxyphenyl)-2-naphthoic acid. The interaction of 6-(4-methoxyphenyl)-2-naphthoic acid/ethyl ester and the 3-adamantyl analogs with DNA was studied in aqueous solution at physiological conditions by UV-vis spectroscopy. The calculated binding constants K(ligand-DNA) ranged between 1.1×10(4) M(-1) and 1.1×10(5) M(-1), the higher values corresponding to those of the adamantylated compounds. Molecular modeling studies have emphasized that the intercalative binding of adapalene and its derivatives to DNA is mainly stabilized by hydrophobic interactions related to the presence of the adamantyl group.
6-[3-(1-金刚烷基)-4-甲氧基苯基]-2-萘甲酸（阿达帕林），一种对 RARβ 和 RARγ 受体具有特异性的合成芳香维甲酸，已通过在钯/碳介导的 Suzuki 偶联反应中由 6-溴-2-萘甲酸和 4-甲氧基苯硼酸之间制备得到，然后在形成的 6-(4-甲氧基苯基）-2-萘甲酸的 3 位引入金刚烷基。在生理条件下的水溶液中，通过紫外可见光谱研究了 6-(4-甲氧基苯基）-2-萘甲酸/乙酯和 3-金刚烷基类似物与 DNA 的相互作用。计算的结合常数 K（配体-DNA）范围在 1.1×10(4) M(-1) 至 1.1×10(5) M(-1) 之间，较高的值对应于金刚烷基化合物的值。分子建模研究强调了阿达帕林及其衍生物与 DNA 的插入结合主要通过与金刚烷基存在相关的疏水性相互作用来稳定。
