Mechanistic Studies of Arene-Ruthenium(II) Complexes with Carbothioamidopyrazoles as Alternative Cancer Drugs.

Arene-ruthenium(II) complexes with carbothioamidopyrazoles at the C-2 and C-5 positions have been recognized as chemotherapeutic agent alternatives to cisplatin and its oxaliplatin analogs. The aim of this study was to continue research on the biological aspect of arene-ruthenium(II) complexes and their anticancer activity. The present paper includes an additional 12 new tumor cells, analyzed by MTT, and employs a series of extended bioassays to better understand their potential mechanism of antitumor activity. The following tests were conducted: membrane permeability studies, intramolecular reactive oxygen and nitrogen species (ROS/RNS) assays, mitochondrial potential changes, DNA analysis by comet assay using the electrophoresis method, measurement of cleaved PARP protein levels, and determination of apoptotic and necrotic cell fractions by fluorescence microscopy. Additionally, the article presents lipophilicity studies based on RP-TLC and molecular docking studies. We hope that the presented data will prove useful in practical treatment, especially for patients with cancer.

Arene-Ruthenium(II) Complexes with Carbothiamidopyrazoles as a Potential Alternative for Antibiotic Resistance in Human.

To meet the demand for alternatives to commonly used antibiotics, this paper evaluates the antimicrobial potential of arene-ruthenium(II) complexes and their salts, which may be of value in antibacterial treatment. Their antimicrobial activity (MIC, MBC/MFC) was examined in vitro against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Pseudomonas aeruginosa, Proteus vulgaris and Candida albicans and compared with classic antibiotics used as therapeutics. Selected arene-ruthenium(II) complexes were found to have synergistic effects with oxacillin and vancomycin against staphylococci. Their bactericidal effect was found to be associated with cell lysis and the ability to cut microbial DNA. To confirm the safety of the tested arene-ruthenium(II) complexes in vivo, their cytotoxicity was also investigated against normal human foreskin fibroblasts (HFF-1). In addition, the antioxidant and thus pro-health potential of the compounds, i.e., their nonenzymatic antioxidant capacity (NEAC), was determined by two different methods: ferric-TPTZ complex and DPPH assay.

Anticancer and antimicrobial properties of novel η6-p-cymene ruthenium(ii) complexes containing a N,S-type ligand, their structural and theoretical characterization.

Ruthenium(ii) complexes are lately of great scientific interest due to their chemotherapeutic potential as anticancer and antimicrobial agents. Here we present the synthesis of new pyrazole carbothioamide derivatives and their four arene-ruthenium complexes. The title compounds were characterized with the application of IR, NMR, mass spectrometry, elemental analysis and X-ray diffraction. Additionally, for new complexes DFT calculations were done. Their antimicrobial activity (MIC, MBC/MFC) was examined in vitro against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Pseudomonas aeruginosa, Proteus vulgaris and Candida albicans. Their cytotoxic effects, using the MTT assay, against three cancer cell lines: HL-60, NALM-6, WM-115 and normal human foreskin fibroblasts (HFF-1) were also investigated. The influence of the new arene-ruthenium(ii) complexes on the DNA structure was also tested. From our results, compound 2d showed higher cytotoxicity against melanoma cell line WM-115 than cisplatin. Strong biostatic and biocidal activity of the tested complexes against Gram-positive bacteria, including S. aureus, S. epidermidis and E. faecalis was demonstrated. The new arene-ruthenium(ii) compounds could not only inhibit proliferation of cancer cells, but also protect patients against malignant wound infections.

Antimicrobial and Structural Properties of Metal Ions Complexes with Thiosemicarbazide Motif and Related Heterocyclic Compounds.

Antibiotic resistance acquired by various bacterial fungal and viral pathogens poses therapeutic problems of increasing severity. Among the infections that are very difficult to treat, biofilm-associated cases are one of the most hazardous. Complex structure of a biofilm and unique physiology of the biofilm cells contribute to their extremely high resistance to environmental conditions, antimicrobial agents and the mechanisms of host immune response. Therefore, the biofilm formation, especially by multidrugresistant pathogens, is a serious medical problem, playing a pivotal role in the development of chronic and recurrent infections. These factors create a limitation for using traditional chemiotherapeutics and contribute to a request for development of new approaches for treatment of infectious diseases. Therefore, early reports on antimicrobial activity of several complexes of metal ions, bearing thiosemicarbazide or thiosemicarbazones as the ligands, gave a boost to worldwide search for new, more efficient compounds of this class, to be used as alternatives to commonly known drugs. In general, depending on the presence of other heteroatoms, these ligands may function in a di-, tri- or tetradentate forms (e.g., of N,S,-, N,N,S-, N,N,N,S-, N,N,S,S-, or N,S,O-type), which impose different coordination geometries to the resultant complexes. In the first part of this review, we describe the ways of synthesis and the structures of the ligands based on the thiosemicarbazone motif, while the second part deals with the antimicrobial activity of their complexes with selected metal ions.