Cu^II and Au^III Complexes with Glycoconjugated Dithiocarbamato Ligands for Potential Applications in Targeted Chemotherapy

Abstract

This work is focused on the synthesis, characterization, and preliminary biological evaluation of bio‐conjugated AuIII and CuII complexes with the aim of overcoming the well‐known side effects of chemotherapy by improving the selective accumulation of an anticancer metal payload in malignant cells. For this purpose, carbohydrates were chosen as targeting agents, exploiting the Warburg effect that accounts for the overexpression of glucose‐transporter proteins (in particular GLUTs) in the phospholipid bilayer of most neoplastic cells. We linked the dithiocarbamato moiety to the C1 position of three different monosaccharides: d‐glucose, d‐galactose, and d‐mannose. Altogether, six complexes with a 1:2 metal‐to‐ligand stoichiometry were synthesized and in vitro tested as anticancer agents. One of them showed high cytotoxic activity toward the HCT116 colorectal human carcinoma cell line, paving the way to future in vivo studies aimed at evaluating the role of carbohydrates in the selective delivery of whole molecules into cancerous cells.

Role of Copper on Mitochondrial Function and Metabolism

“…Cu(II) ion increases the activity of 8-hydroxyquinoline derivatives in inhibiting the chymotrypsin-like activity of the proteasome and induces growth inhibition and apoptosis ( Oliveri et al, 2017 ). The Cu(II) ion complex with glycoconjugate DTC shows potential applications in targeted chemotherapy; in particular, the CuGlu ([CuII(DTC-β- d -glucose)2]) revealed an exciting IC50 (2.0 ± 0.1 µM) value for the HCT116 human colorectal carcinoma cell line ( Pettenuzzo et al, 2019 ). Estrogen-functionalized Cu(II) complexes are potent anticancer agents with low IC50 values.…”

The Ca2+-ATPase Inhibition Potential of Gold(I, III) Compounds

“…Thus, it was described that several inorganic compounds and complexes present Ca 2+ -ATPases IC 50 inhibition values globally not so different from the above well-known Ca 2+ -ATPases drugs inhibitors, for example decavanadate (IC 50 = 15 µM), polyoxotungstates (IC 50 = 0.3-200 µM), polyoxovanadates (IC 50 =1 µM), and vanadium complexes such as BMOV (IC 50 = 40 µM), among others [31][32][33][34][35]. In summary, both gold(I) and gold(III) compounds 1-4 are strong inhibitors of the SR Ca 2+ -ATPase, pointing out this enzyme as a putative target for gold compounds with anticancer activity, described as promising agents for the future in medicinal chemistry [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]23,29,[42][43][44].…”

Emerging Molecular Receptors for the Specific-Target Delivery of Ruthenium and Gold Complexes into Cancer Cells

“…An extensive number of inorganic and organometallic gold and ruthenium complexes have been conjugated to several different biomolecules for targeted anticancer purposes. These include systems targeting the amino acid transporters [ 102 , 106 , 107 , 108 , 109 ], peptide transporters [ 110 , 111 ], glucose transporters [ 69 , 112 , 113 ], and vitamin transporters [ 77 , 114 , 115 , 116 , 117 , 118 ]. As our review mainly focuses on the emerging receptors for the target delivery of ruthenium and gold complexes into cancer cells, for which the use of biomolecules as delivering carriers is well-known and is out of our scope, we will not discuss them in further detail.…”