Chiral amino acid–based anthraquinones: synthesis, structural characterization, and structure–activity relationships in cancer cell lines

Abstract

A new family of chiral amino acid-based anthraquinones has been synthesized and fully characterized by multinuclear magnetic resonance (1H, 13C and 15N), elemental analysis, UV–Vis spectroscopy, circular dichroism, single-crystal X-ray diffraction and infrared spectroscopy. These molecules have been studied in different cancer cell lines (PANC-1, MCF-7, A549, SF268, HCT116) and a non-tumoral cell line (L-929) through different in vitro assays. The results showed that these molecules had dose-dependent antitumor effects, with compound 4e showing the lowest IC50 values across most tumor cell lines. Its crystal structure confirmed the enantiomeric purity and revealed π–π stacking interactions between anthraquinone and phenylalanine rings, features that may contribute to its enhanced biological performance. In addition, it was observed that the compounds had the ability to decrease cell migration and clonogenicity in the treated cell lines, demonstrating their ability to inhibit tumor malignancy processes. After studying possible molecular routes through which they induce their effect, it was shown that they are capable of inducing apoptosis and that they do not cause intracellular damage through the production of ROS. Therefore, these new synthesized compounds showed therapeutic potential in cancer, although further study of the molecular mechanisms involved in this antitumor activity is still needed.