Oxidised juncuenin B analogues with increased antiproliferative activity on human adherent cell lines: semisynthesis and biological evaluation

Juncuenin B is a phenanthrene belonging to a relatively small group of plant secondary metabolites. Phenanthrenes have become of great interest in the last 20 years because of their wide-range of structural and pharmacological diversity like antioxidant, anti-inflammatory, antimicrobial and antiproliferative activities [1].

Protoflavones are a unique, relatively oxidized class of flavonoids. They bear a non-saturated B-ring, and a hydroxyl group is connected through C-1ʹ. These flavonoid analogues with a para-quinol ring are described in the literature with considerable antiproliferative activities [2].

The aim of our work was to merge the characteristics of the mentioned metabolites, according to the structural similarities of phenanthrenes and flavonoids. As juncuenin B contains phenolic hydroxyl groups, during oxidation reactions formation of p-quinol ring containing semisynthetic derivatives were expected. To accomplish these reactions, organic oxidizing agents, namely PIFA ([bis(trifluoroacetoxy)iodo]benzene) and PIDA [(diacetoxyiodo)benzene] were applied under different reaction conditions. From the reaction mixtures, thirteen compounds were prepared by using combined chromatographic techniques (prep. TLC, MPLC, and HPLC). The components are substituted with methoxy-, ethoxy-, and butoxy groups; majority of them contain a p-quinol ring. The structure elucidation of the compounds was carried out by 1D and 2D NMR spectroscopic methods. The antiproliferative activity of the compounds was investigated on different human cancer (MCF-7, T47d, HeLa, SiHa, C33a, and A2780) and mouse embryo fibroblast cell lines. Five compounds possessed remarkable inhibition [IC₅₀ values 1.93–30.03 μM] on the tested cell lines, higher than the original compound, juncuenin B.

• References

• 1 Tóth B, Hohmann J, Vasas A. Phenanthrenes: a promising group of plant secondary metabolites. J Nat Prod 2018; 81: 661-668
• 2 Hunyadi A, Martins A, Danko B, Chang FR, Wu YC. Protoflavones: a class of unusual flavonoids as promising novel anticancer agents. Phytochem Rev 2014; 13: 69-77