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Description
Monocarbonyl analogs of curcumin (MACs) containing α,β-unsaturated carbonyl systems are electrophilic compounds capable of interacting with thiol-containing nucleophiles via thia-Michael addition.1,2 Their reactivity toward biologically relevant thiols, such as N-acetylcysteine, is important for understanding their chemical behavior and potential biological activity. In this study, we investigated the spectrophotometric kinetic behavior of two 2-fluorobenzylidene monocarbonyl analogs of curcumin, EF24 [(3E,5E)-3,5-bis(2-fluorobenzylidene)-4-piperidone] and 2FCXNON [(2E,6E)-3,6-bis(2-fluorobenzylidene) cyclohexanone], in the presence of N-acetylcysteine.
The reactions were followed by UV/VIS spectroscopy using N-acetylcysteine in excess to ensure complete reaction based on literature data.1,2 Both compounds were examined in DMSO and in 100 mM aqueous phosphate buffer/acetonitrile, 80:20 v/v (pH 7.4). Reactions were monitored for 6 h in DMSO and for approximately 30 min in the buffered medium, where faster spectral changes were observed.
EF24 showed time-dependent spectral changes in DMSO and a faster response in phosphate buffer/acetonitrile, indicating higher reactivity toward N-acetylcysteine under buffered conditions. In contrast, 2FCXNON showed no significant spectral changes in either medium under the applied experimental conditions. The reactivity of EF24 and 2FCXNON toward N-acetylcysteine was evaluated, providing preliminary kinetic data. The developed UV/VIS method is simple, reproducible, and suitable for comparative assessment of the thiol-reactivity of other MACs.
Keywords: monocarbonyl analogs of curcumin, fluorinated MACs, N-acetylcysteine, thia-Michael addition, UV/VIS kinetics, phosphate buffer.
References:
1. Amslinger, S.; Al-Rifai, N.; Winter, K.; Wörmann, K.; Scholz, R.; Baumeister, P.; Wild, M. Reactivity assessment of chalcones by a kinetic thiol assay. Org. Biomol. Chem. 2013, 11, 549–554. https://doi.org/10.1039/C2OB27163J.
2. Clariano, M.; Marques, V.; Vaz, J.; Awam, S.; Afonso, M. B.; Perry, M. J.; Rodrigues, C. M. P. Monocarbonyl analogs of curcumin with potential to treat colorectal cancer. Chem. Biodivers. 2023, 20, e202300222. https://doi.org/10.1002/cbdv.202300222.;