Novel Ruthenium(II) and Gold(I) NHC Complexes: Synthesis, Characterization, and Evaluation of Their Anticancer Properties

Abstract

The synthesis, characterization, and biological evaluation of novel Ru(II)-and Au(I)-N-heterocyclic carbenes is reported. The NHC-ruthenium(II) complexes (1−6) were synthesized by reacting the appropriately substituted imidazolium bromides with Ag 2 O, forming the NHC-silver bromide in situ followed by transmetalation with dimeric p-cymene ruthenium(II) dichloride. In an analogous manner the NHCgold(I) chloride complexes (NHC-Au(I)Cl) 7−9 were synthesized, utilizing dimethylsulfido gold(I) chloride as the transmetalating agent. The ligand exchange on the NHCgold(I) chlorides was achieved by either reacting the complexes with silver acetate to yield the NHC-gold(I) acetates (NHC-Au(I)OAc) 10−12 or reacting the NHC-gold(I) chlorides under basic conditions with 2′,3′,4′,6′-tetra-O-acetyl-1-thio-β-D-glucopyranose (SR) to give the NHC-gold(I)-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyl-1-thiolate) complexes (NHC-Au(I)SR) 13−15. The Ru(II)-NHC complex 1 and the Au(I)-NHC complex 9 were characterized by single-crystal X-ray diffraction. Also the IC 50 values of these 15 complexes were determined by an MTT-based assay against the human cancer cell lines Caki-1 (renal) and MCF-7 (breast). The Ru(II) complexes 1−6 revealed the following IC 50 values against Caki-1 of >500, 94 (±5), 93 (±2), 170 (±20), 39 (±5), and 13 (±2) μM and against

N -Heterocyclic Carbene Metal Complexes as Bio-Organometallic Antimicrobial and Anticancer Drugs

“…Surprisingly ruthenium(II) benzimidazolylidene carbene complexes with inadequate cellular uptake 111a-c showed a little efficacy toward tumor cell growth at the highest studied concentration. The synthesis, characterization and biological evaluation of novel NHC-ruthenium(II) complexes 112, 113a-e ( Figure 12) have been reported by Tacke et al All the NHC-ruthenium(II) complexes were synthesized by reacting the appropriately substituted imidazoliumbromides with Ag 2 O, forming the NHC-silver bromide in situ followed by transmetalation with dimeric p-cymeneruthenium(II) dichloride [136]. The IC 50 values of the complexes 112 and 113a-e against the human cancer cell lines Caki-1 (renal) and MCF-7 (breast) have revealed moderateto-good results [136].…”

“…[147] 109b 0.31 ± 0.08 A2780 [147] 109c 0.12 ± 0.02 A2780 [147] 109d 4.82 ± 0.12 A2780 [147] 109e 41.0 ± 8.2 A2780 [147] 109f 0.21 ± 0.05 A2780 [147] 109a 25.6 ± 5.5 A2780R [147] 109b 1.77 ± 0.04 A2780R [147] 109c 0.23 ± 0.02 A2780R [147] 109d 37.8 ± 7.8 A2780R [147] 109e >200 A2780R [147] 109f 1.10 ± 0.12 A2780R [147] 109a 435 ± 25 HEK [147] 109b 29.0 ± 1.8 HEK [147] 109c 1.80 ± 0.20 HEK [147] 109d 64.0 ± 6.1 HEK [147] 109e >200 HEK [147] 109f 1.85 ± 0.12 HEK [147] 110 0.06 ± 0.0076 A549 [148] 110 1.25 ± 0.12 HCT116 [148] 110 0.1 ± 0.032 MCF7 [148] 111a >100 MCF7 112 >500 Caki-1 [136] 112 >500 MCF-7 [136] 113a 94 ± 5 Caki-1 [136] 113a 80 ± 15 MCF-7 [136] 113b 93 ± 2 Caki-1 [136] 113b 19 ±1 MCF-7 [136] 113c 170 ± 20 Caki-1 [136] 113c 7.1 ± 1.2 MCF-7 [136] 113d 39 ± 5 Caki-1 [136] 113d 2.4 ± 0.7 MCF-7 [136] 113e 13 ± 2 Caki-1 [136] 113e 7.0 ± 1.2 MCF-7 [136] 1 Fish RH, Jaouen G. Bioorganometallic chemistry: structural diversity of organometallic complexes with bioligands and molecular recognition studies of several supramolecular hosts with biomolecules, alkali-metal ions, and organometallic pharmaceuticals. Organometallics 22 (11), 2166-2177 (2003).…”

“…The obtained NHC-gold(I) complexes 87-91 have been tested for their antiproliferative effects in human ovarian cancer A2780 cells, and in nontumorigenic human embryonic kidney HEK-293T cells, showing promising anticancer properties and a certain selectivity toward cancerous cells. Three NHC-gold(I) chloride 92a-c, three NHC-gold(I)acetate 93a-c and three NHC-gold(I)SR (SR = 2′,3′,4′,6′-tetra-O-acetyl-1-thio-β-D-glucopyranose) 94a-c complexes reported by Tacke et al [136]. The IC 50 values of the NHC-gold complexes 92a-c to 94a-c against the human cancer cell lines Caki-1 (renal) and MCF-7 (breast) have revealed moderate-to-good results, with complexes 92a, 94a and 94b showing low micromolar activity against MCF-7.…”

“…Caki-1 14 (±2) [136] 94b Caki-1 17 (±2) [136] 94c Caki-1 58 (±2) [136] 92a MCF-7 8.4 (±0.4) [136] 92b MCF-7 30 (±3) [136] 92c MCF-7 12 (±1) [136] 93a MCF-7 23 (±3) [136] 93b MCF-7 12 (±1) [136] 93c MCF-7 25 (±3) [136] 94a MCF-7 6.1 (±1.5) [136] 94b MCF-7 9.3 (±1.6) [136] 94c MCF-7 14 (±2) [136] ( [113] (Figure 9). All the complexes showed cytotoxic activity with IC 50 in the micromolar range and distinct selectivity for certain cell lines.…”

Metal-based glycoconjugates and their potential in targeted anticancer chemotherapy

“…Hackenberg et al reported on the anticancer activity of NHC-carbene analogues of auranofin in which the alkyl substituents on the carbene were specifically modified (Au-8) [122]. Cytotoxicity studies were encouraging especially in human MCF7 breast adenocarcinoma and Caki-1 skin carcinoma cells, in particular in comparison to analogues where either the carbene or the thioglucose ligands are replaced by chlorides.…”