Synthesis and anticancer activity of carbosilane metallodendrimers based on arene ruthenium(ii) complexes

Abstract

A series of new organometallic carbosilane dendrimers (first and second generation) and the corresponding non-dendritic mononuclear based on ruthenium arene fragments are described. The metallodendrimers were prepared by reaction of precursor [Ru(η6-p-cymene)Cl2]2 with carbosilane dendrimers functionalized with N- donor monodentate ligands such as NH2- and pyridine, or with N,O-, N,N- chelating imine ligands. While the dendrimer precursors are insoluble in DMSO or water, novel metallodendrimers are soluble in DMSO and some of them are even highly soluble in water. The molecular structure of the “Ru-NH2” mononuclear compound (zero generation) was determined by single-crystal X-ray crystallography. The cytotoxicity activity of these dendritic structures was evaluated in several human cancer cell lines and compared with that of the corresponding mononuclear ruthenium complexes. Most compounds display significant cytotoxic activities in the low micromolar range with the first generation ruthenium dendrimers being the most active compounds. The cell death type for selected compounds has been studied along with their reactivity towards relevant biomolecules such as DNA, Human Serum Albumin (HSA) and Cathepsin-B. All the data points to a mode of action different from that of cisplatin for most complexes. First generation ruthenium dendrimers inhibit Cathepsin-B which may suggest potential antimetastatic properties of these compounds.

Combination of Ruthenium Dendrimers and Acoustically Propelled Gold Nanowires as a Platform for Active Intracellular Drug Delivery Towards Breast Cancer Therapy

“…The main idea of this work was to prepare and characterize a novel nanomotor-based platform suitable for higher payload and accelerated drug delivery towards cancer cells. We were focused to newly synthesized carbosilane dendrimers with ruthenium arene fragments [1]. Carbosilane dendrimers are water-soluble, monodisperse and stable molecules that are able to carry various therapeutically active compounds and genes as previously described [2].…”

“…Fluorescently labeled dendrimer (FITC-CRD13) was synthetized at the Organic and Inorganic Chemistry Department, University Alcala, Spain. Detailed synthesis of CRD13 and its heterofunctional rutheniumterminated carbosilane dendrimer with FITC (FITC-CRD13) are described in [1,4]. FITC-CRD13 with molecular weight 2234,66 g/mol was dissolved in H2O/DMSO (9/1) solution at 1 mM concentration and stored in the dark condition at 4°C before use.…”

“…Dendrimers are highly branched nanoparticles with unique molecular properties, which make them promising carriers for delivery of various therapeutically active compounds into the disease affected cells. Recently, a new class of carbosilane metallodendrimers based on ruthenium (CRD) possessing anticancer activity has been synthesized [1][2][3][4]. At the same time, another group of engineered nanostructures named gold nanowires (AuNWs) have been intensively studied during the last years as active intracellular transporters (nanomotors) when placed under ultrasound (US) fields [5][6][7].…”

Cytotoxic Activity and Structure–Activity Relationship of Triazole‐Containing Bis(Aryl Ether) Macrocycles

“…The World Health Organization estimates that 8.2 million deaths in 2011 were due to cancer, whereas other reports now consider it to be the second highest cause of death worldwide . Mortality in cancer occurs if metastases cause deterioration of vital organs, which leads to an impaired function of the biological systems …”

“…[3] Mortality in cancero ccurs if metastases cause deterioration of vital organs, whichl eads to an impaired function of the biological systems. [4] Despite the important advances in medicine and molecular genetics, the search for novel therapeutic agents for cancer treatment is ongoing. [5] Macrocyclic structures, both naturally occurring and synthetic, have recently been recognized as novel alternatives for cancert reatment.…”