Exploiting natural products to build metalla-assemblies: the anticancer activity of embelin-derived Rh(III) and Ir(III) metalla-rectangles.
Six new pentamethylcyclopentadienyl Rh(III) and Ir(III) metalla-rectangles ([3](CF3SO3)4-[8](CF3SO3)4) have been prepared by a self-assembly strategy using the embelin-derived metalla-clips (η5-C5Me5)2M2(μ4-C6HRO4-κO)Cl2 (M = Rh, 1; M = Ir, 2; R = (CH2)10CH3) 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.
Institute of Chemistry, University of Neuchatel, Avenue de Bellevaux 51, CH-2000 Neuchatel, Switzerland. gajendra.gupta@unine.ch.
Gajendra
G
Gupta
CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Habsiguda, Hyderabad-500 007, India. mahesh73@ccmb.res.in.
Jerald Mahesh
JM
Kumar
Institute of Chemistry, University of Neuchatel, Avenue de Bellevaux 51, CH-2000 Neuchatel, Switzerland. amine.garci@unine.ch.
Amine
A
Garci
CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Habsiguda, Hyderabad-500 007, India. mahesh73@ccmb.res.in.
Narayana
N
Nagesh
Institute of Chemistry, University of Neuchatel, Avenue de Bellevaux 51, CH-2000 Neuchatel, Switzerland. bruno.therrien@unine.ch.
Bruno
B
Therrien
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016227:Benzoquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D057809:HEK293 Cells; D006801:Humans; D007495:Iridium / Q000737:chemistry / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008024:Ligands; D012238:Rhodium / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D016227:Benzoquinones; D001688:Biological Products; D056831:Coordination Complexes; D008024:Ligands; D007495:Iridium; D012238:Rhodium; C010945:embelin