Exploiting Natural Products to Build Metalla-Assemblies: The Anticancer Activity of Embelin-Derived Rh(III) and Ir(III) Metalla-Rectangles

Abstract

Abstract:Six new pentamethylcyclopentadienyl Rh(III) and Ir(III) metalla-rectangles ([3](CF 3 SO 3 ) 4 -[8](CF 3 SO 3 ) 4 ) have been prepared by a self-assembly strategy using the embelin-derived metalla-clips (η 5 -C 5 Me 5 ) 2 M 2 (μ 4 -C 6 HRO 4 -κO)Cl 2 (M = Rh, 1; M = Ir, 2; R = (CH 2 ) 10 CH 3 ) and the linear ditopic ligands, pyrazine, 4,4'-bipyridine and 1,2-bis (4-pyridyl)ethylene. These new metalla-rectangles have been obtained in high yield and isolated as their triflate salts. The complexes have been fully characterized by standard spectroscopic techniques and the antiproliferative activity of these tetranuclear complexes was evaluated in vitro on cancerous (DU-145, A-549, HeLa) and noncancerous (HEK-293) cell lines. The biological study has showed a better activity for the rhodium derivatives over the iridium analogs and for all complexes a very good selectivity for cancerous over noncancerous cells. The presence of lipophilic side chains coupled with the positive charge of the tetranuclear complexes suggested a cytotoxic activity involving the mitochondrial machinery, as demonstrated by multiple biological experiments.

Increasing the selectivity of biologically active tetranuclear arene ruthenium assemblies

“…These four doublets and two singlets confirm the presence of two isomers (Fig. 2), as previously observed in the analogous tetranuclear complexes, [(h 5 -Cp*) 4 Rh 4 (m 4 -embelin) 2 (m 2 -bpy) 2 ](CF 3 SO 3 ) 4 and [(h 5 -Cp*) 4 Rh 4 (m 4 -embelin) 2 (m 2 -bpe) 2 ](CF 3 SO 3 ) 4 [12]. Indeed, in these metalla-cycles the alkyl chains of the embelin units can either be positioned cis or trans from each other.…”

Self‐Assembled BODIPY‐Based Iridium Metallarectangles: Cytotoxicity and Propensity to Bind Biomolecules

“…Iridium complexes have recently gained popularity because of their antiproliferative activities against cancer cell lines of different origins . Human cervical cancer (HeLa) and glioblastoma (U87) cells were incubated with increasing doses (0–50 μ m ) of 3 and 4 .…”

“…An important example is auranofin, which displays potent in vitro and in vivo anticancer properties . Iridium‐based complexes have not been tested as potential drug candidates as extensively as their ruthenium counterparts . Iridium(III) is one of the most inert low‐spin d 6 ‐metal ions, but its inertness also depends on other ligands used in complexation.…”

The Application of Embelin for Cancer Prevention and Therapy

“…In another recent report, embelin-derived rhodium Rh(III) and iridium Ir(III) metalla-rectangles derivatives inhibited the growth of DU-145 prostate cancer, A-549 lung cancer, and cervical cancer HeLa cells. In contrast there was a minimal effect on the growth of non-cancerous HEK-293 cells [ 125 ].…”