Synthesis, characterization, theoretical studies and antioxidant and cytotoxic evaluation of a series of Tetrahydrocurcumin (THC)-b enzylate d derivatives

The benzylation reaction of curcumin and tetrahydrocurcumin (THC) with benzyl bromide and potassium carbonate in acetone was investigated. It was found that curcumin undergoes O-alkylation first, followed by C-1 substitution. In contrast, THC undergoes these reactions in reverse order, which was further ex-plained by DFT calculations showing a clear energetic preference (19.5 Kcal/mol) for the C-1 versus the O-alkylation reaction of THC. In addition, the antioxidant activities on lipid peroxidation and cytotoxic activities of both benzylated derivatives were studied, showing that the C-dibenzylated curcuminoid (C-DiBn, 2b ), exerts a superior activity than both tribenzylated (TriBn, 2c ) and tetrabenzylated (TetraBn, 2d ) curcuminoid derivatives in both essays. A DFT theoretical study to explain the experimental results and the preferences for the nucleophilic attack between the phenolic oxygen or C-1 anions was conducted. Furthermore, docking calculations on a DNA fragment shed light on the potential factors affecting the biological activity of these benzylated curcuminoids.(c) 2022 Elsevier B.V. All rights reserved.

Automated summary

This study investigated the benzylation reaction of curcumin and tetrahydrocurcumin with benzyl bromide and potassium carbonate in acetone. It was found that curcumin undergoes O-alkylation first, followed by C-1 substitution, while THC undergoes these reactions in reverse order. The antioxidant and cytotoxic activities of the benzylated derivatives were studied, and the C-dibenzylated curcuminoid showed superior activity compared to the tribenzylated and tetrabenzylated derivatives. DFT calculations and docking calculations on a DNA fragment were conducted to explain the experimental results and the preferences for nucleophilic attack.