Halochromic Behavior and Anticancer Effect of New Synthetic Anthocyanidins Complexed with β-Cyclodextrin Derivatives

Abstract

Anthocyanidins, the aglycons of anthocyanins, are known, beyond their function in plants, also as compounds with a wide range of biological and pharmacological activities, including cytostatic effect against various cancer cells. The nature and position of the substituents in the flavylium cation is essential for such biological properties, as well as the equilibrium between the multistate of the different chemical species that are generated by the flavylium cation, including quinoidal base, hemiketal, and cis- and trans-chalcones. In this work, eight new flavylium derivatives were synthesized, characterized for confirmation of the structure by FT-IR and 2D-NMR, and investigated in vitro as possible cytostatic compounds against HCT116 and HepG2 cancer cells. The most active two compounds were explored for their halochromic properties that can influence the biological activity and subjected to molecular encapsulation in β-cyclodextrin derivatives in order to increase their solubility in water and bioavailability. The anticancer effect was influenced by the position (6-, 7-, or 8-) of the methoxy group in the β-ring of the methoxy-4’-hydroxy-3’-methoxyflavylium cation, while the study of the halochromic properties revealed the important role played by the chalcone species of the pH-dependent multistate in both the uncomplexed and inclusion complex forms of these anthocyanidins.

Anticancer Activity of Chalcones and Its Derivatives: Review and In Silico Studies

“…In addition, the compounds in studies still showed Topoisomerase I and II inhibitory activity [ 33 ]. Based on the properties of anthocyanidins and aglycones, Păușescu and collaborators (2022) [ 34 ] carried out a synthesis of derivatives of the flavilium cation (7) ( Figure 5 ), these being evaluated for anticancer activities in HCT116 and HepG2 strains. The anticancer effect was influenced by the position (6-, 7-, or 8-) of the methoxy group on the β-ring for the methoxy-4′-hydroxy-3′ methoxyflavilyl cation.…”

“…In addition, the compounds in studies still showed Topoisomerase I and II inhibitory activity [33]. Based on the properties of anthocyanidins and aglycones, Păușescu and collaborators (2022) [34] carried out a synthesis of deriva- In a study carried out in 2019, Hashid and collaborators [32] observed that chalcones that have hydroxy, methoxy, and chlorine groups in the ortho and para positions, have strong inhibitory actions against mechanisms of inflammatory action, such as inhibition of cyclooxygenase. It was also revealed in this study that treatment with these compounds was able to inhibit up to 90% of inflammatory edemas.…”

“…In addition, pyrazolone aldehydes were produced using the Vilsmeier-Haack reaction, via the reaction between aldehydes and ketones in an alcoholic medium with sodium hydroxide. The in vitro assays were combined with in silico simulations that demonstrated high affinity of the compounds under study with mediators such as interleukins, as it was also possible to observe that the in vitro cell viability studies of the series show that chalcones (34), (35), and (36) (Figure 8) presented IC50 values of 2.96, 2.97, and 2.82 µM against CAl27 oral cancer cell lines.…”

Synthesis, Characterization, and Antiproliferative Properties of New Bio-Inspired Xanthylium Derivatives

“…Polyphenols and their synthetic analogs interfere in carcinogenesis by modulating and regulating multiple signaling pathways and transcription factors, membrane-associated receptor tyrosine kinases, fatty acid metabolism and lipid rafts or methylation, together with other emerging targets [ 5 ]. Various synthetic analogues of natural polyphenols demonstrated strong anticancer activity, including (–)-epigallocatechin-3-gallate analogues [ 6 ], synthetic anthocyanidins [ 7 ], or cinnamic acid derivatives [ 8 ]. Some analogues with known anticarcinogenic effect proved even higher stability to metabolic conversion and displayed comparable or higher antitumor activity than the parent compound [ 9 ].…”