Synthesis and in vitro Toxicity of d‐Glucose and d‐Fructose Conjugated Curcumin–Ruthenium Complexes

Abstract

A series of carbohydrate‐conjugated bis(demethoxy)curcumin (BDC) ligands were synthesized by using the Huisgen copper(I)‐catalyzed cycloaddition between azido‐functionalized d‐glucose and d‐fructose as well as propargyl‐modified BDC. The unprotected sugar ligands were treated with Ru(bpy)2Cl2 to form curcumin‐conjugated Ru complexes of general formula Ru(bpy)2(L)Cl. The ligands as well as Ru complexes were analyzed by NMR, IR, UV/Vis, and fluorescence spectroscopy, mass spectrometry as well as by elemental analysis (EA). Incubation of L929, HepG2 and the breast cancer cell line MDA‐MB‐231 revealed lower cytotoxicity of all carbohydrate‐conjugated ligands compared with BDC. The Ru complexes exhibited higher cytotoxicity than the parent ligands, in particular against HepG2 cells, whereas the noncancerous L929 cell line remained unaffected. Unexpectedly, the d‐fructose‐conjugated ligand and its corresponding Ru complex did not show any significant toxicity against MDA‐MB‐231 cells.

Curcumin Diglutaric Acid, a Prodrug of Curcumin Reduces Pain Hypersensitivity in Chronic Constriction Injury of Sciatic Nerve Induced-Neuropathy in Mice

“…Therefore, several approaches and formulation strategies have been used to improve the oral bioavailability of curcumin, such as nanoformulation, adjuvants, and prodrugs [ 9 , 15 , 16 , 17 , 18 ]. The prodrug approach for improving physicochemical and pharmacokinetic properties of curcumin includes conjugating curcumin with polymers [ 19 ], sugars [ 20 ], amino acids [ 21 ], retinoic acid [ 22 ], fatty acids [ 23 ], and dicarboxylic acids, such as succinic acid [ 24 , 25 ] and diglutaric acid [ 26 ].…”

Glycoconjugated Metal Complexes as Cancer Diagnostic and Therapeutic Agents

“…in 2016, reported an appealing study on the synthesis of curcumin sugar‐based ligands to coordinate Ru(II) complexes in order to exploit the combined chemotherapy action of two bioactive compounds, the metal complex and the diaryl‐hepanoid curcumin (Figure 31). [96] Medical applications of curcumin and its derivatives, in fact, were limited by some major drawbacks, such as rapid metabolism, and poor solubility in water; but after coordination with metal complexes, the final compounds resulted more soluble in aqueous solution, more photo‐cytotoxic [97] and showed an increased cytotoxicity by intercalation. Furthermore, the addition of carbohydrates to the curcumin skeleton in metal complexes ( 88 a and 88 b , Figure 31) enhanced both the solubility and the cellular uptake in cancer cells.…”

Transporter and protease mediated delivery of platinum complexes for precision oncology

“…While the reductive activation of platinum(IV) complexes and the potency of the platinum(II) products that result gives it unique advantages, there is every reason to investigate similar targeting strategies for other metals, particularly since some of these are potentially more potent. Albumin targeted delivery of an iridium complex has recently been reported demonstrated promising light activation dependent cytotoxicity [85] while glucose transporter targeted delivery of ruthenium complexes was less promising [86]. Peptide conjugates of a wide variety of organometallic agents have been described [87] and some of these have potential to be transporter mediated agents with selectivity against cells that overexpress the relevant transporter.…”