Is the Way to Fight Cancer Paved with Gold? Metal-Based Carbene Complexes with Multiple and Fascinating Biological Features

Abstract

Herein, we report the synthesis and the multiple anti-tumor properties of new gold and silver carbene complexes. The chemical modifications, grounded on our previous studies, led us to identify a good lead complex, gold-based, whose biological features are very exciting and promising in the anti-cancer research and could be further developed. Indeed, the bis-[4,5-dichloro-(N-methyl-N’(2-hydroxy-2-phenyl)ethyl-imidazole-2-ylidene)gold(I)]+[dichloro-gold]− (AuL7) complex possesses the ability to interfere with at least three important and different intracellular targets, namely the human topoisomerases I and II and tubulin, which are able to modulate metabolic processes not directly correlated each other. We proved that the modifications of the ligands structure in AuL7, with respect to another already published complex, i.e., bis-[4,5-dichloro-(N-methyl-N’(cyclopentane-2ol)-imidazole-2-ylidine)gold(I)]+[dichloro-gold]− (AuL4), produce a different behavior toward tubulin-polymerization process, since AuL7 is a tubulin-polymerization inhibitor and AuL4 a stabilizer, with the final same result of hampering the tumor growth. Taken together, our outcomes designate AuL7 as a promising compound for the development of multi-targeted anti-cancer therapies.

α–ω Alkenyl‐bis‐S‐Guanidine Thiourea Dihydrobromide Affects HeLa Cell Growth Hampering Tubulin Polymerization

“…Tubulin polymerization inhibition was evaluated using an in vitro tubulin Polymerization Assay Kit purchased from EMD Millipore, employing the manufacturer's instructions with some modifications. [6,47] Briefly, polymerization reactions were realized in 70 μL final volumes, in which 60 μL is represented by the 60 μM tubulin in 1x PB-GTP and 10 μL contain the tested molecules dissolved in the same buffer. Paclitaxel, vinblastine and nocodazole (used as controls) and each tested compound are dissolved in DMSO and used at final concentration of 10 μM.…”

A Review on the Advancements in the Field of Metal Complexes with Schiff Bases as Antiproliferative Agents

“…These compounds form highly stable complexes with transition metal ions [2]. Metal complexes in which the metal is coordinated to different ligands, able to stabilize the metal and modify its chemical and pharmaceutical properties, have gained considerable importance in medicinal chemistry [3] as antitumor agents [4][5][6][7]. Complexes containing the transition metals platinum, gold and silver have attracted much attention due to their antitumor effects.…”

Electromagnetically Stimuli-Responsive Nanoparticles-Based Systems for Biomedical Applications: Recent Advances and Future Perspectives

“…Secondly, high efficiencies can be obtained with reduced amounts of drugs in the human body: This a very relevant aspect, especially for drugs with high cytotoxicity (e.g., chemotherapy). For antitumor therapies, in fact, the research is mainly focused on two directions: One is the development of new molecules [ 12 , 13 , 14 , 15 ], and the other is the development of completely different systems, such as nanoparticles, hybrid materials, and fibrous membranes, that are able to carry active molecules or fight against cancer [ 16 , 17 , 18 , 19 ]. This latter aspect has determined a spreading interest in nanoparticles for antitumor treatment and in the biomedical field.…”