Metal–Curcumin Complexes in Therapeutics: An Approach to Enhance Pharmacological Effects of Curcumin

Abstract

Curcumin, an active component of the rhizome turmeric, has gained much attention as a plant-based compound with pleiotropic pharmacological properties. It possesses anti-inflammatory, antioxidant, hypoglycemic, antimicrobial, neuroprotective, and immunomodulatory activities. However, the health-promoting utility of curcumin is constrained due to its hydrophobic nature, water insolubility, poor bioavailability, rapid metabolism, and systemic elimination. Therefore, an innovative stride was taken, and complexes of metals with curcumin have been synthesized. Curcumin usually reacts with metals through the β-diketone moiety to generate metal–curcumin complexes. It is well established that curcumin strongly chelates several metal ions, including boron, cobalt, copper, gallium, gadolinium, gold, lanthanum, manganese, nickel, iron, palladium, platinum, ruthenium, silver, vanadium, and zinc. In this review, the pharmacological, chemopreventive, and therapeutic activities of metal–curcumin complexes are discussed. Metal–curcumin complexes increase the solubility, cellular uptake, and bioavailability and improve the antioxidant, anti-inflammatory, antimicrobial, and antiviral effects of curcumin. Metal–curcumin complexes have also demonstrated efficacy against various chronic diseases, including cancer, arthritis, osteoporosis, and neurological disorders such as Alzheimer’s disease. These biological activities of metal–curcumin complexes were associated with the modulation of inflammatory mediators, transcription factors, protein kinases, antiapoptotic proteins, lipid peroxidation, and antioxidant enzymes. In addition, metal–curcumin complexes have shown usefulness in biological imaging and radioimaging. The future use of metal–curcumin complexes may represent a new approach in the prevention and treatment of chronic diseases.

Alzheimer’s Disease and Diabetes Mellitus in Comparison: The Therapeutic Efficacy of the Vanadium Compound

“…The results derived from the mouse model robustly proved that the vanadium compounds were beneficial for the central nervous system [ 137 ], and could be considered as potential drugs for curing AD [ 11 , 12 , 138 ]. In addition, another vanadium compound, bis-[curcumino]oxovanadium (BCOV) [ 139 ], which was synthesized by curcumino and oxovanadium, also displayed protective effects on diabetes mellitus [ 140 ]. It was shown that BCOV could reduce the serum LDL level significantly in obese rats [ 140 ].…”

Natural Product-Based Hybrids as Potential Candidates for the Treatment of Cancer: Focus on Curcumin and Resveratrol

“…Molecules 2021, 26, 4665 4 of 33 ketol-enol group fosters the formation of stable metal-Cur complexes, which have been recently comprehensibly reviewed elsewhere [33]. As said before and recently reviewed by several authors [21,24,34,35], Cur has been shown to target all the main steps of cancer development, being capable of interfering with several biochemical pathways involved in the proliferation and survival of cancer cells as well as directly and indirectly binding different targets.…”

“…This latter feature, coupled with the unsaturated nature of the C 7 chain with trans C=C, gives rise to a planar and linear structure for Cur with the methoxy groups pointed out in the opposite direction with respect to the 1,3-keto-enol group, according to prior crystal X-ray diffraction studies [ 32 ]. Moreover, the presence of the 1,3-ketol-enol group fosters the formation of stable metal–Cur complexes, which have been recently comprehensibly reviewed elsewhere [ 33 ]. As said before and recently reviewed by several authors [ 21 , 24 , 34 , 35 ], Cur has been shown to target all the main steps of cancer development, being capable of interfering with several biochemical pathways involved in the proliferation and survival of cancer cells as well as directly and indirectly binding different targets.…”

“…First, a traditional approach is represented by the design of metal–polyphenol complexes. This is easily evident for Cur, which bears an α,β-unsaturated β-diketo moiety with keto–enol isomerization in its chemical structure and thus can readily form a complex with many transition and nontransition metal ions, rare earth ions, and metal oxides, which may help increase its solubility and stability [ 33 ]. Metals usually bind to the keto–enol group of Cur by chelation, generally in the ratio 1:1 or 1:2 metal/Cur (although the binding of three Cur molecules has also been reported).…”

Circulating Tumour Cells (CTCs) in NSCLC: From Prognosis to Therapy Design

“…Targeting iron homeostasis with flavonoid chelators such as quercetin has been intensively studied in anticancer treatment and is usually highly specific for cancer cells [363]. The anticancer effects of curcuminoids are also associated with iron chelation [364,365]. Nevertheless, higher levels of transition metal ions can lead to higher levels of flavonoids and curcumin metal complexes.…”