Curcuminoid Chalcones: Synthesis, Stability, and New Neuroprotective and Sonosensitising Activities

Abstract

The primary purpose of this work was to design and obtain a series of curcuminoid chalcone–NSAID hybrid derivatives. The ester-type hybrid compounds with ibuprofen (i), ketoprofen (ii), and naproxen (iii) were obtained in two ways, using the Claisen–Schmidt reaction and the Steglich esterification reaction. The designed molecules were successfully synthesised, and FT-IR, MS, and NMR spectroscopy confirmed their structures. Moreover, the cytotoxic effect of the sonodynamic therapy and the anti-inflammatory, antioxidant, and anticholinergic properties of some curcuminoid chalcones and curcuminoid chalcones hybrids were evaluated. The curcuminoid chalcone derivatives showed promising neuroprotective activity as sonosensitisers for sonodynamic therapy in the studied cell lines. Additionally, the stability of the ester-type hybrid compounds with promising activity was determined. The RP-HPLC method was used to observe the degradation of the tested compounds. Studies have shown that structural isomers of ester-type hybrid compounds (3ai, 3bi) are characterised by a similar susceptibility to degradation factors, i.e., they are extremely unstable in alkaline environments, very unstable in acidic environments, unstable in neutral environments, practically stable in oxidising environments, and photolabile in solutions and in the solid phase. These compounds maintain adequate stability in environment at pH 1.2 and 6.8, which may make them good candidates for developing formulations for oral administration.

Chain branching during the polycondensation of isophthalic aldehyde and 1,1′‐diacetylferrocene by the Claisen–Schmidt reaction

“…The low-molecular weight chalcones are among the available compounds and can be obtained by acid-catalyzed croton condensation or by the Claisen-Schmidt reaction (base-catalyzed croton condensation). 4,[12][13][14][15][16] The activity of chalcones containing a conjugated enone fragment in photochemical [2 + 2] cycloaddition reactions has made it possible to synthesize a number of polymers that are capable of cross-linking in very mild conditions under UV radiation and are promising as mesogens, photoresists, and lithographic materials. [17][18][19] In the mentioned cases the chalcone fragment was part of the side groups, and a linear polymer capable of subsequent photochemical cross-linking was formed as a result of the polymerization of vinyloxycarbonyl chalcones 19 or methacroyl chalcones.…”