Ufa Institute of Chemistry of the Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, Russia.
Chem Biol Drug Des. 2024 Sep;104(3):e14632. doi: 10.1111/cbdd.14632.
In search for new molecules of diterpene origin with promising anticancer activity, two amino-derivatives (methyl maleopimarate aminoimide and methyl 1β,13-epoxydihydroquinopimarate C4-hydrazone) were involved in the 4-component Ugi reaction (Ugi-4CR) and pseudo-7-component azido-Ugi condensation (azido-Ugi-7CR) to afford a series of adducts holding α-aminoacylamide and bis-1,5-disubstituted tetrazole substituents. The NCI-60 cancer cell panel screening revealed diterpene-type Ugi adducts 2, 5, and 6 with strong antiproliferative potency with GI in range of 1.2-15.4 μM. The high positive correlations with standard anticancer drugs suggest microtubules or progesterone and androgen receptors as possible targets of the synthesized compounds.
为了寻找具有潜在抗癌活性的新二萜类化合物，我们将两种氨基酸衍生物（马来酸甲酯氨基亚胺和 1β,13-环氧二氢松香酸甲酯 C4-腙）引入到 4 组分 Ugi 反应（Ugi-4CR）和假 7 组分叠氮 Ugi 缩合（azido-Ugi-7CR）中，得到一系列含有α-氨基酰基酰胺和双 1,5-取代四唑取代基的加合物。NCI-60 癌细胞系筛选结果表明，二萜型 Ugi 加合物 2、5 和 6 具有很强的增殖抑制活性，GI 值在 1.2-15.4 μM 范围内。与标准抗癌药物的高度正相关表明微管或孕激素和雄激素受体可能是合成化合物的作用靶点。
