The semi-synthetic process of curcumin mono-zerumbonyl ether derivatives with anti-inflammatory, cytotoxic, and antimicrobial effects has been validated.

Abstract

The invention proposes a semi-synthetic and isolation procedure for a curcumin mono-zerumbonyl ether derivative via structural coupling reaction between curcumin and 3-bromozerumbone. The procedure involves bromination of zerumbone with N-bromosuccinimide, followed by etherification with curcumin at a 1:1 molar ratio in N,N-dimethylformamide solvent under K2CO3 catalysis at room temperature. The extracted reaction mixture is purified in multiple steps by silica gel column chromatography (n-hexane and acetone system in a 1.5:1 ratio) and RP-18 reversed-phase column chromatography (methanol and water system in a 3:7 ratio) to specifically isolate the monosubstituted derivative. Selective shielding of a phenolic hydroxyl group by the zerumbone group improves lipophilicity and maintains the spatial flexibility of the molecule. The obtained curcumin mono-zerumbonyl ether compound is used as the active ingredient in pharmaceutical preparations.In vitro test results showed that the compound effectively inhibited nitric oxide (NO) production in RAW 264.7 macrophages with an IC50 value of 32.15 µg / ml, caused cytotoxicity in Hep-G2 liver cancer cells with an IC50 of 25.35 µg / ml, and inhibited 6 out of 8 tested microorganisms with MIC values ​​ranging from 100 µg / ml to 200 µg / ml.