Daidzein, a naturally occurring isoflavone phytoestrogen, exhibits dual estrogenic and anti-estrogenic properties,making it a promising candidate for anticancer research. However, its poor solubility, rapid metabolism, and limited bioavailability hinder its therapeutic potential. To overcome these drawbacks, two novel derivatives of the isoflavones were synthesized: 7-O-carboxymethyl-4′‑hydroxy-2-trifluoromethylisoflavone 5b and 7-O-carboxymethyl-4′-hydroxyisoflavone 5a. Single crystal X-ray diffraction analysis of 3b and 5b offered perspectives on their molecular architecture, revealing key O…H, F…H, C…O, and C…H interactions critical for molecular packing. Hirshfeld surface analysis further highlighted signifcant intermolecular forces influencing crystal stability. Biological evaluations demonstrated that compounds 5a and 5b selectively inhibited HT-29 colorectal cancer cells, with IC50 values of 20.99 and 14.30 μM, respectively, while exhibiting only moderate effects on B16F10 melanoma cells and minimal toxicity toward normal MEF-1 cells. Incorporating a CF₃ moiety in 5b signifcantly enhanced its antiproliferative activity. These fndings suggest that fluorinated isoflavone derivatives hold promise as selective anticancer agents with improved bioavailability and anticancer efficacy.

Title

Synthesis of 7-O-carboxymethylisoflavones, x-ray structure, Hirshfeld analysis, and anticancer activity assessment

Publisher

Journal of Molecular Structure

Publisher Country

Netherlands

Indexing

Scopus

Impact Factor

4.7

Publication Type

Online only

Volume

1357

Year

2026

Pages

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