Abstract

Usnic acid has anti-cancer activity, however, low solubility and toxicity limit the potential. To investigate biological activity of usnic acid derivatives, enantiopure derivatives were synthesised by reacting usnic acid with ethylenediamine, which yielded one dimer product ((+)-1), and two tetra cyclic compounds ((+)-2 and (-)-2). The products were characterised with NMR, and evaluated in vitro in human colon cancer cell line Caco-2 by cell count, phase-contrast microscopy, MTT-assay, measurement of DNA content and cell cycle distribution. All compounds tested showed cytostatic effect in Caco-2 cells, but each compound had a distinct cellular effect. Compound (+)-1 showed anti-proliferative activity by increasing the percentage of cells in S-phase with 25% compared to the control. Compounds (+)-2 and (-)-2 induced paraptosis, but only compound (+)-2 modulated cell cycle distribution by accumulating cells in G₂/M-phase by 47% and reduced DNA content by 60%. All compounds express interesting cellular and potential anti-proliferative activity.

摘要

松萝酸具有抗癌活性，但溶解度低和毒性限制了其潜力。为了研究松萝酸衍生物的生物活性，通过松萝酸与乙二胺反应合成了对映体纯衍生物，得到一种二聚体产物 ((+)- 1 ) 和两种四环化合物 ((+)- 2和 (-)- 2 )）。产品通过核磁共振进行表征，并通过细胞计数、相差显微镜、MTT 测定、DNA 含量和细胞周期分布的测量在人结肠癌细胞系 Caco-2 中进行体外评估。所有测试的化合物在 Caco-2 细胞中都显示出细胞抑制作用，但每种化合物都具有不同的细胞作用。化合物 (+)- 1与对照相比，S 期细胞的百分比增加了 25%，从而显示出抗增殖活性。化合物(+)- 2和(-)- 2诱导了细胞凋亡，但只有化合物(+)- 2通过在G ₂ /M 期积累细胞47% 和减少DNA 含量60% 来调节细胞周期分布。所有化合物都表现出有趣的细胞和潜在的抗增殖活性。