Synthesis of First Copper Metal Complex of C=C Extended Curcuminoid Analogue: Structure, β-Cyclodextrin Association, and Biological Properties

Tavera-Hernández, Rosario; Sánchez-Obregón, Rubén; Obregón-Mendoza, Marco A.; Nieto-Camacho, Antonio; Ramírez-Apan, María Teresa; Pérez-González, Leidys L.; Enríquez, Raúl G.

doi:10.3390/molecules30193943

Open AccessArticle

Synthesis of First Copper Metal Complex of C=C Extended Curcuminoid Analogue: Structure, β-Cyclodextrin Association, and Biological Properties

by

Rosario Tavera-Hernández

^*

,

Rubén Sánchez-Obregón

,

Marco A. Obregón-Mendoza

^*

,

Antonio Nieto-Camacho

,

María Teresa Ramírez-Apan

,

Leidys L. Pérez-González

and

Raúl G. Enríquez

^*

Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Mexico City 04510, Mexico

^*

Authors to whom correspondence should be addressed.

Molecules 2025, 30(19), 3943; https://doi.org/10.3390/molecules30193943

Submission received: 4 September 2025 / Revised: 20 September 2025 / Accepted: 21 September 2025 / Published: 1 October 2025

(This article belongs to the Special Issue Advances in Phenolic Based Complexes)

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Abstract

The search for bioactive compounds against chronic diseases such as cancer and diabetes includes curcuminoids as promising scaffolds. Here, we report the synthesis of a family of curcuminoid analogue compounds with an extended unsaturated central chain, as follows: difluoroboron complex 1, the enolised curcuminoid 2, and its homoleptic copper complex 3, in moderate to good yields (68–90%). Additionally, their β-cyclodextrin (BCD) association complexes, 4 and 5, were prepared through a mechanochemical method and characterised by spectroscopic techniques. Complete ¹H and ¹³C NMR assignments and NOESY correlations revealed unique solvent effects on the conformational disposition of compound 2, while the copper complex 3 displayed the highest extinction coefficient (1.20 × 10⁵ M⁻¹·cm⁻¹). Furthermore, the authentication of the polymorph of 1 and the new crystal structures of 2 and 3, determined by single-crystal X-ray analysis, were highlighted. Although the copper complex 3 initially exhibited the lowest a-glucosidase inhibitory activity (IC₅₀ > 100 µM), it showed a significant increase (IC₅₀ = 36.27 µM) upon association with BCD, reaching values comparable to the free ligand (IC₅₀ = 45.63 µM). Compounds 1–5 were non-toxic to healthy cells (COS-7), but compound 5 stands out as a promising candidate against this metabolic condition.

Keywords: analogue curcuminoid; copper complex; single-crystal structure; π-elongated chain; β-cyclodextrin complex; α-glucosidase

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MDPI and ACS Style

Tavera-Hernández, R.; Sánchez-Obregón, R.; Obregón-Mendoza, M.A.; Nieto-Camacho, A.; Ramírez-Apan, M.T.; Pérez-González, L.L.; Enríquez, R.G. Synthesis of First Copper Metal Complex of C=C Extended Curcuminoid Analogue: Structure, β-Cyclodextrin Association, and Biological Properties. Molecules 2025, 30, 3943. https://doi.org/10.3390/molecules30193943

AMA Style

Tavera-Hernández R, Sánchez-Obregón R, Obregón-Mendoza MA, Nieto-Camacho A, Ramírez-Apan MT, Pérez-González LL, Enríquez RG. Synthesis of First Copper Metal Complex of C=C Extended Curcuminoid Analogue: Structure, β-Cyclodextrin Association, and Biological Properties. Molecules. 2025; 30(19):3943. https://doi.org/10.3390/molecules30193943

Chicago/Turabian Style

Tavera-Hernández, Rosario, Rubén Sánchez-Obregón, Marco A. Obregón-Mendoza, Antonio Nieto-Camacho, María Teresa Ramírez-Apan, Leidys L. Pérez-González, and Raúl G. Enríquez. 2025. "Synthesis of First Copper Metal Complex of C=C Extended Curcuminoid Analogue: Structure, β-Cyclodextrin Association, and Biological Properties" Molecules 30, no. 19: 3943. https://doi.org/10.3390/molecules30193943

APA Style

Tavera-Hernández, R., Sánchez-Obregón, R., Obregón-Mendoza, M. A., Nieto-Camacho, A., Ramírez-Apan, M. T., Pérez-González, L. L., & Enríquez, R. G. (2025). Synthesis of First Copper Metal Complex of C=C Extended Curcuminoid Analogue: Structure, β-Cyclodextrin Association, and Biological Properties. Molecules, 30(19), 3943. https://doi.org/10.3390/molecules30193943

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Synthesis of First Copper Metal Complex of C=C Extended Curcuminoid Analogue: Structure, β-Cyclodextrin Association, and Biological Properties

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