An increasing number of novel Ru(II) polypyridyl complexes have been successfully applied as photosensitizers (PSs) for photodynamic therapy (PDT). Despite recent advances in optimized PSs with refined photophysical properties, the lack of tumoral selectivity is often a major hurdle for their clinical development. Here, classical maleimide and versatile NHS‐activated acrylamide strategies were employed to site‐selectively conjugate a promising Ru(II) polypyridyl complex to the N‐terminally Cys‐modified Bombesin (BBN) targeting unit. Surprisingly, the decreased cell uptake of these novel Ru‐BBN conjugates in cancer cells did not hamper the high phototoxic activity of the Ru‐containing bioconjugates and even decreased the toxicity of the constructs in the absence of light irradiation. Overall, although deceiving in terms of selectivity, our new bioconjugates could still be useful for advanced cancer treatment due to their nontoxicity in the dark.

This study was designed to propose alternative therapeutic compounds to fight against bacterial pathogens. Thus, a library of nitrogen-based compounds bis(triazolyl)methane (1T–7T) and bis(pyrazolyl)methane (1P–11P) was synthesised following previously reported methodologies and their antibacterial activity was tested using the collection strains of Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa. Moreover, the novel compound 2P was fully characterized by IR, UV–Vis and NMR spectroscopy. To evaluate antibacterial activity, minimal inhibitory concentrations (MICs), minimal bactericidal concentrations (MBCs), minimum biofilm inhibitory concentrations (MBICs), and minimum biofilm eradication concentrations (MBECs) assays were carried out at different concentrations (2–2000 µg/mL). The MTT assay and Resazurin viability assays were performed in both human liver carcinoma HepG2 and human colorectal adenocarcinoma Caco-2 cell lines at 48 h. Of all the synthesised compounds, 2P had an inhibitory effect on Gram-positive strains, especially against S. aureus. The MIC and MBC of 2P were 62.5 and 2000 µg/mL against S. aureus, and 250 and 2000 µg/mL against E. faecalis, respectively. However, these values were > 2000 µg/mL against E. coli and P. aeruginosa. In addition, the MBICs and MBECs of 2P against S. aureus were 125 and > 2000 µg/mL, respectively, whereas these values were > 2000 µg/mL against E. faecalis, E. coli, and P. aeruginosa. On the other hand, concentrations up to 250 µg/mL of 2P were non-toxic doses for eukaryotic cell cultures. Thus, according to the obtained results, the 2P nitrogen-based compound showed a promising anti-Gram-positive effect (especially against S. aureus) both on planktonic state and biofilm, at non-toxic concentrations.

Breast cancer is the second leading cause of cancer death worldwide. Despite progress in drug discovery, identification of the correct population is the limiting factor to develop new compounds in the clinical setting. Therefore, the aim of this study is to evaluate the effects of a new metallodrug, [RuCl( p -cymene)( N , N -bis(diphenylphosphino)-isopropylamine)][BF 4 ] ( pnpRu-14 ), as a lead pnp-Ru compound by screening and preliminary biochemical and biological studies in different breast cancer subtypes. The results show that complex pnpRu-14 is much more effective in promoting in vitro cytotoxic effects on HER2+ and RH+/HER2– breast cancer than the reference metallodrugs cisplatin, carboplatin, or RAPTA-C. It is important to highlight that pnpRu-14 shows an impressive cytotoxicity against BT474 cells. Caspase-dependent apoptosis is the mechanism of action for these compounds. In addition, treatment of SKBR3, BT474, T47D, and MCF7 cancer cells with pnpRu-14 caused an accumulation of cells in the G0/G1 phase cells. The human serum albumin, DNA, and H1 histones binding properties of the lead compound are reported. Pharmacokinetic and biodistribution studies show a quick absorption of pnpRu-14 in serum with no significant accumulation in any of the tested organs. This work provides evidence to support the preclinical and clinical development of pnpRu-14 in breast cancer.

Objective: The purpose of this study was to evaluate the in vitro antibacterial effects of a p-Cymene-based bis(pyrazolyl)methane derivative to advance in developing alternative therapeutic compounds to fight against bacterial isolates from patients with otitis externa (OE). Methods: Eighteen swab specimens were collected from patients aged over 18 years diagnosed with OE within at least 7 days of symptom onset, contaminated by only one bacterium type: Pseudomonas aeruginosa (n = 5); Staphylococcus aureus (n = 8); Klebsiella aerogenes (n = 2); Serratia marcescens (n = 1); Morganella morganii (n = 2). To appraise antibacterial activity, minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC), and minimum biofilm eradication concentration (MBEC) assays were run at different SC-19 concentrations.Results: When using SC-19, S. aureus strains showed less bacterial growth, but no bactericidal effect was observed. The MIC and MBC of SC-19 were 62.5 and 2000 μg/ml against S. aureus and were >2000 μg/ml against the other isolates obtained from OE, respectively. In addition, the MBICs and MBECs of SC-19 against S. aureus were 125 and >2000 μg/ml, respectively. Conclusion:Nowadays the acquired antibiotic resistance phenomenon has stimulated research into novel and more efficient therapeutic agents. Hence, we report that, helped by the structural diversity fostered herein by a range of bis(pyrazolyl)methane derivatives, SC-19 can be a promising alternative therapeutic option for treating OE caused by S. aureus given the observed effects on both planktonic state and biofilm.