Synthesis, Structural Characterization, and Antiproliferative Activity of Bi(III), In(III), Ga(III), Sb(III), and Te(IV) Coordination Compounds of Umbelliferone in Breast Cancer Cells

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Abstract
Umbelliferone (7-hydroxycoumarin) is a bioactive scaffold whose pharmacological profile may be modified through coordination to metal centers. Five coordination compounds of umbelliferone with the main-group elements Bi(III), In(III), Ga(III), Sb(III), and Te(IV) were synthesized by alkali-assisted deprotonation of the phenolic group followed by reaction with the corresponding metal salt, and characterized by melting point, FT-IR, 1H and 13C NMR spectroscopy, FAB+ mass spectrometry, and elemental microanalysis. Disappearance of the phenolic ν(O–H) band (3113 cm−1) and of the 1H signal at 10.5 ppm in U-Bi, U-In, U-Ga and U-Te, with a minor residual signal persisting for U-Sb, together with preservation of the aromatic and vinylic resonances of the coumarin core and a shift in ν(C=O) from 1701 cm to 1 to 1667–1683 cm−1, is consistent with metal binding through the C7-phenolato oxygen. Antiproliferative activity and cytotoxicity were evaluated in MCF-7 and MDA-MB-231 breast cancer cells and in non-tumorigenic MCF-10A cells at 24 and 48 h, by crystal violet (CV) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. The coordination compounds displayed metal- and cell-line-dependent activity relative to free umbelliferone. U-Te (IC50 = 7.4 µM) and U-Sb (9.5 µM) were the most potent in MCF-7 cells, while U-Bi (9.8 µM) was the most active in MDA-MB-231 cells, all at 24 h. IC50 values in MCF-10A cells were ≥181 µM for every compound at 24 h, yielding selectivity indices >17 for the most active members of the series. Treated tumor cells showed morphological changes consistent with cytotoxicity (rounding, loss of adhesion, and monolayer disruption). These findings identify U-Sb, U-Te, and U-Bi as the most active and selective compounds of the series and support further investigation of umbelliferone-derived coordination compounds as potential antiproliferative agents. However, further investigation is needed to determine the relative contributions of intact compounds and solution-derived species to the observed biological effects.
Funding Information
  • Secretaría de Ciencia, Humanidades, Tecnología e Innovación (CBF2023-2024-3937)
  • Secretaría de Ciencia, Humanidades, Tecnología e Innovación (4003291)

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