Cytotoxicity studies of water soluble coordination compounds with a [Mo2O2S2]2+ core

Abstract

Selected molybdenum sulfur compounds with the formulas (M)[Mo2O2S4L] where (Et4N)2(1), L=S4(2-), (Et4N)(2), L=Cp, (3), L=DMF, K(5), L=serine, M=Et4N(+), K(+), Na(+) and [Mo2O2S2L2] where Na2(4), L=cysteine, and (6), L=threonine, were prepared and subjected to cytotoxicity studies in vitro. The results were analyzed to rank the compounds according to their relative cytotoxicity and to correlate the observed toxicity to specific composition. The results guide future efforts to synthesize highly water soluble, non-toxic, compounds. Strong correlation was observed between toxicity and cation selection, as well as selection of biocompatible ligands combined with alkali metal salts. The most toxic compound analyzed showed about 50 times less cytotoxicity than the cisplatin reference compound in HT-29 cells. Preliminary results from in vivo data agree with the ranking obtained in vitro.

Screening of biological properties of MoV2O2S2- and MoV2O4-based coordination complexes: Investigation of antibacterial, antifungal, antioxidative and antitumoral activities versus growing of Spirulina platensis biomass

“…These findings reveal the importance of the counter cation on the overall toxicity and show that molybdenum(V) [Mo2O2S2] 2+ and [Mo2O4] 2+ moieties coordinated with biocompatible ligands are non-toxic. This is in good agreement with other cytotoxicity results related to Mo2O2S2-based complexes associated to NEt4 + or alkali cations reported in the literature [24].…”

“…Their convenient low cytotoxicity on cells was considered useful for possible therapeutic applications like the development of catalytic drugs. [24] In the last two decades, we acquired a strong expertise in the chemistry of such dimolybdic cores, which are used in the domain of polyoxometalates as building block for the synthesis of supramolecular assemblies, [25,26] some of them being capable of exhibiting electrocatalytic properties for the reduction of protons. [27,28] Furthermore, more recently we have patented results showing that such complexes can stimulate activity of microalgae Spirulina platensis.…”

Impact of Molybdenum Compounds as Anticancer Agents

“…Organomolybdenum compounds can be referred to coordinated molybdenum compounds in various oxidation states. They are potent anticancer and antimicrobial agents [8, 9, 17–19, 24–26]. According to Nair et al, biological applications of molybdenum complexes were due to the ability of incorporated ligands to chelate with trace metal ion (molybdenum ion), their rare action mechanisms, and capability to produce a high amount of harmful reactive oxygen species (ROS) which can interrupt the redox balance of a system leading to increase in deoxyribonucleic acid (DNA) damage, DNA protein cross-linked formation, lipid peroxidation, cellular toxicity, and/or wrong initiation of cellular signaling paths [8].…”

Water-Soluble α-Amino Acid Complexes of Molybdenum as Potential Antidotes for Cyanide Poisoning: Synthesis and Catalytic Studies of Threonine, Methionine, Serine, and Leucine Complexes

“…Transition metal complexes able to catalyze the reaction of cyanide and sulfur donor substrates (e.g., thiosulfate) are an attractive option in the development of novel emergency treatments for cyanide poisoning in vivo . The development of catalytic molybdenum metallodrugs to supplement rhodanase places the need for a low cytotoxicity and good physical properties, such as the water solubility of the potential therapies, at the forefront of challenges to overcome. , The selection of ligands and counter cations for the molybdenum complexes affect both the solubility and toxicity of the potential treatment …”

“…Ligand substitution of the DMF by nontoxic and water-soluble α-amino acid ligands (α-aa) decreases the toxicity of the molybdenum complexes and increases the water solubility. Sodium and potassium salts are relatively nontoxic compared to complexes with alkylammonium salts and show a higher water solubility . Molybdenum–sulfur complexes with water-soluble α-amino acid ligands and Na + or K + counter cations are therefore an attractive option to achieve biocompatibility.…”