Synthesis, characterization, anti-inflammatory and anti-proliferative activity against MCF-7 cells of O-alkyl and O-acyl flavonoid derivatives

• Six O-alkyl flavonoid derivatives including two novel compounds were synthesized with two alkylation reagents.
• Seven O-acyl flavonoid derivatives including a novel compound were synthesized with two acylation reagents.
• Effect of structure of flavonoid on hydroxyl group reactivity at 5-position was showed.
• Anti-inflammatory activity of all flavonoids was examined by in vitro and in vivo.
• Anti-proliferative activity of all flavonoids was examined by SRB assay and apoptosis.

A series of O-alkyl and O-acyl flavonoid derivatives was synthesized in high efficiency. Alkylation and acylation of 5-hydroxyflavonoids showed that the low reactivity hydroxyl group, 5-OH, well reacted with strong reagents whereas with weaker reagents, the different products were obtained dependently on structural characteristic of ring C of respective flavonoid. In order to evaluate anti-inflammatory activity, all compounds were tested for in vitro inhibition of bovine serum albumin denaturation and in vivo inhibition of carrageenan-induced mouse paw edema. Among them, the compounds 3, 3b, 4b and 4c demonstrated more effective anti-inflammatory activity than standard drugs (diclofenac sodium and ketoprofen) in both tests. Meanwhile, the flavonoids 2, 2c, 3a and 4b displayed anti-proliferative activity against MCF-7 cell lines. Triacetyl derivative of hesperetin 4b inducing degradation of DNA in MCF-7 cells was observed.

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