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

TL;DR

Scientists synthesized a new copper complex of a curcuminoid compound and found it has potential for treating metabolic diseases like diabetes.

Contribution

The novel copper complex of an extended curcuminoid analogue and its β-cyclodextrin association are newly synthesized and characterized.

Findings

The copper complex 3 showed a high extinction coefficient and improved α-glucosidase inhibition when associated with β-cyclodextrin.

Compound 5 was identified as a promising candidate for metabolic conditions without toxicity to healthy cells.

Crystal structures of the compounds were determined using single-crystal X-ray analysis.

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.

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