The successful design of antitumour drugs often combines in one molecule different biologically active subunits that can affect various regulatory pathways in the cell and thus achieve higher efficacy. Two ferrocene derivatives, DK-164 and CC-78, with different residues were tested for cytotoxic potential on non-small lung cancer cell lines, A549 and H1299, and non-cancerous MRC5. DK-164 demonstrated remarkable selectivity toward cancer cells and more pronounced cytotoxicity against A549. The cytotoxicity of CC-78 toward H1299 was even higher than that of the well-established anticancer drugs cisplatin and tamoxifen, but it did not reveal any noticeable selective effect. DK-164 showed predominantly pro-apoptotic activity in non-small cell lung carcinoma (NSCLC) cells, while CC-78 caused accidental cell death with features characteristic of necrosis. The level of induced autophagy was similar for both substances in cancer cells. DK-164 treatment of A549, H1299, and MRC5 cells for 48 h significantly increased the fluorescence signal of the NFkB (nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells) protein in the nucleus in all three cell lines, while CC-78 did not provoke NFkB translocation in any of the tested cell lines. Both compounds caused a significant transfer of the p53 protein in the nucleus of A549 cells but not in non-cancerous MRC5 cells. In A549, DK-164 generated oxidative stress close to the positive control after 48 h, while CC-78 had a moderate effect on the cellular redox status. In the non-cancerous cells, MRC5, both compounds produced ROS similar to the positive control for the same incubation period. The different results related to the cytotoxic potential of DK-164 and CC-78 associated with the examined cellular mechanisms induced in lung cancer cells might be used to conclude the specific functions of the various functional groups in the ferrocene compounds, which can offer new perspectives for the design of antitumour drugs.

We performed synthesis of new nitrofuranyl amides and investigated their anti-TB activity and primary genetic response of mycobacteria through whole-genome sequencing (WGS) of spontaneous resistant mutants. The in vitro activity was assessed on reference strain Mycobacterium tuberculosis H37Rv. The most active compound 11 was used for in vitro selection of spontaneous resistant mutants. The same mutations in six genes were detected in bacterial cultures grown under increased concentrations of 11 (2×, 4×, 8× MIC). The mutant positions were presented as mixed wild type and mutant alleles while increasing the concentration of the compound led to the semi-proportional and significant increase in mutant alleles. The identified genes belong to different categories and pathways. Some of them were previously reported as mediating drug resistance or drug tolerance, and counteracting oxidative and nitrosative stress, in particular: Rv0224c, fbiC, iniA, and Rv1592c. Gene-set interaction analysis revealed a certain weak interaction for gene pairs Rv1592–Rv1639c and Rv1592–Rv0224c. To conclude, this study experimentally demonstrated a multifaceted primary genetic response of M. tuberculosis to the action of nitrofurans. All three 11-treated subcultures independently presented the same six SNPs, which suggests their non-random occurrence and likely causative relationship between compound action and possible resistance mechanism.

A series of OLED-relevant compounds, consisting of 1,3,5-triazine core linked to various aromatic arms by amino group, has been synthesized and characterized. The studied compounds exist in solution as a mixture of two conformers, a symmetric propeller and asymmetric conformer, in which one of the aromatic arms is rotated around the C-N bond. At temperatures below −40 °C, the VT NMR spectra in DMF-d7 are in a slow exchange regime, and the signals of two conformers can be elucidated. At temperatures above 100 °C, the VT NMR spectra in DMSO-d6 are in a fast exchange regime, and the averaged spectra can be measured. The ratio of symmetric and asymmetric conformers in DMF-d7 varies from 14:86 to 50:50 depending on the substituents. The rotational barriers of symmetric and asymmetric conformers in DMF-d7 were measured for all compounds and are in the interval from 11.7 to 14.7 kcal/mol. The ground-state energy landscapes of the studied compounds, obtained by DFT calculations, show good agreement with the experimental rotational barriers. The DFT calculations reveal that the observed chemical exchange occurs by the rotation around the C(1,3,5-triazine)-N bond. Although some of the compounds are potentially tautomeric, the measured absorption and emission spectra do not indicate proton transfer neither in the ground nor in the excited state.

Background/Objectives: New anti-tuberculosis compounds are needed to treat patients infected with multi- or extensively drug-resistant Mycobacterium tuberculosis strains. Studies based on spontaneous in vitro mutagenesis can provide insights into the possible modes of action and resistance mechanisms of such new compounds. We evaluated the primary response of M. tuberculosis in vitro to the action of new aroylhydrazones and nitrofuroylamides. Methods: The reference strain H37Rv was cultured on solid media with compounds at increased concentrations relative to MIC. Resistant clones were investigated using whole-genome sequencing and bioinformatics tools to assess the role and potential impact of identified mutations. Results: Some of the mutations are significant (based on in silico analysis), located in essential genes, and therefore of particular interest. Frameshift mutations were observed in (i) Rv2702/ppgK, which is associated with starvation-induced drug tolerance and persistence in mice, and (ii) Rv3696c/glpK, which has been described as a switch on/off mutation associated with drug tolerance. Nonsynonymous substitutions were found in Rv0506/mmpS2, which belongs to the Mmp protein family involved in transport and drug efflux, and in infB, encoding the translation initiation factor IF-2. Conclusions: The primary adaptation of M. tuberculosis to the selective pressure of the tested compounds is complex and multifaceted. It involves multiple unrelated genes and pathways linked to non-specific drug tolerance, efflux systems, or mechanisms counteracting oxidative stress.

p-toluenesulfonic acid (pTSA) was used for the synthesis of porous silica xerogels while applying different synthesis conditions. Key parameters included acid concentration, drying temperature and the method of acid removal. The resulting organic–inorganic composites were investigated by nitrogen physisorption, X-ray powder diffraction (XRD), solid-state NMR and thermal analysis. The results demonstrated that both the drying temperature and quantity of the pTSA significantly influenced the pore structure of the xerogels. The utilization of such strong acids like pTSA yielded high surface area and pore volume, as well as narrow pore size distribution. Environmentally friendly template removal by solvent extraction produced materials with superior textural properties compared to traditional calcination, enabling the recovery and reuse of pTSA with over 95% efficiency. A selected mesoporous silica xerogel was modified by a simple two-step post-synthesis procedure with 1-(2-Hydroxyethyl) piperazine (HEP). High CO₂ adsorption capacity was determined for the HEP-modified material in dynamic conditions. The isosteric heat of adsorption revealed the stronger interaction between functional groups and CO₂ molecules. Total CO₂ desorption could be achieved at 60 °C. Leaching of the silica functional groups could not be detected even after four consecutive adsorption cycles. These findings provide valuable insights into the sustainable synthesis of tunable piperazine-modified mesoporous silica xerogels with potential applications in CO₂ capture.

We report a compelling structure–property relationship in a series of four naphthalimide-derived ligands, engineered for the selective and differential detection of Hg(II) and Cu(II) ions. By integrating a dansyl moiety, we induce intramolecular electron transfer that gives rise to two non-redox-innocent dyad systems. Notably, the detection of Hg(II) operates through a rare chelation-enhanced fluorescence (CHEF) mechanism—an unusual pathway considering the heavy atom effect typically associated with mercury. In contrast, the Cu(II) dyads reveal striking valence tautomerism in solution, driven by ligand-to-metal electron transfer that reduces Cu(II) to Cu(I), as conclusively demonstrated via EPR and XPS analysis. Furthermore, introducing a catalytic substrate probe highlights that this redox transformation is the bottleneck in catalytic efficiency. These findings provide deep mechanistic insights and position these ligands as versatile platforms for dual-mode ion sensing and redox-responsive catalysis.