N-acyl hydrazone (NAH) is recognized as a promising framework in drug design due to its versatility, straightforward synthesis, and attractive range of biological activities, including antimicrobial, antitumoral, analgesic, and anti-inflammatory properties. In the global context of increasing resistance of pathogenic bacteria to antibiotics, NAHs represent potential solutions for developing improved treatment alternatives. Therefore, this research introduces six novel derivatives of (EZ)-N’-benzylidene-2-(6-chloro-9H-carbazol-2-yl)propanehydrazide, synthesized using a microwave-assisted method. In more detail, we joined two pharmacophore fragments in a single molecule, represented by an NSAID-type carprofen structure and a hydrazone-type structure, obtaining a new series of NSAID-N-acyl hydrazone derivatives that were further characterized spectrally using FT-IR, NMR, and HRMS investigations. Additionally, the substances were assessed for their tuberculostatic activity by examining their impact on four strains of M. tuberculosis, including two susceptible to rifampicin (RIF) and isoniazid (INH), one susceptible to RIF and resistant to INH, and one resistant to both RIF and INH. The results of our research highlight the potential of the prepared compounds in fighting against antibiotic-resistant M. tuberculosis strains.

Melanoma is a skin cancer characterized by rapid growth and spread for which current therapies produce both resistance and increased risk of infection. To develop new anti-melanoma biocompatible species, the series of complexes Cu(N-N)(bzac)(X)⋅nH₂O (N-N: 1,10-phenanthroline/2,2′-bipyridine, Hbzac: 1-phenyl-1,3-butanedione, X: NO₃/ClO₄, and n = 0, 1) was studied. Single-crystal X-ray diffraction revealed a mononuclear structure for all complexes. The ability of the complexes to scavenge or trap reactive oxygen species such as O₂⋅⁻ and HO⋅ was proved by EPR spectroscopy experiments. All complexes inhibited B16 murine melanoma cells in a dose-dependent and nanomolar range, but the complexes with 1,10-phenanthroline were more active. Moreover, comparative activity on B16 and healthy BJ cells revealed a therapeutic index of 1.27–2.24. Bioinformatic methods were used to calculate the drug-likeness, pharmacokinetic, pharmacogenomic, and pharmacodynamic profiles of the compounds. The results showed that all compounds exhibit drug-likeness features, as well as promising absorption, distribution, metabolism, and excretion (ADME) properties, and no toxicity. The pharmacodynamics results showed that the neutral species appear to be good candidates for antitumor molecular targets (Tyrosyl-DNA phosphodiesterase 1, DNA-(apurinic or apyrimidinic site) lyase or Kruppel-like factor 5). Furthermore, the pharmacogenomic results showed a good affinity of the copper(II) complexes for the human cytochrome. These results recommend complexes bearing 1,10-phenanthroline as good candidates for developing drugs to melanoma alternative treatment.

Curcumin is a polyphenol of the Curcuma longa plant, which can be used for various medicinal purposes, such as inflammation and cancer treatment. In this context, two symmetric curcumin derivatives (D1—(1E,6E)-1,7-bis(4-acetamidophenyl)hepta-1,6-diene-3,5-dione and D2—p,p-dihydroxy di-cinnamoyl methane) were obtained by the microwave-based method and evaluated for their antitumoral effect on human cervix cancer in comparison with toxicity on non-tumoral cells, taking into account that they were predicted to act as apoptosis agonists or anti-inflammatory agents. The HeLa cell line was incubated for 24 and 72 h with a concentration of 50 μg/mL of derivatives that killed almost half of the cells compared to the control. In contrast, these compounds did not alter the viability of MRC-5 non-tumoral lung fibroblasts until 72 h of incubation. The nitric oxide level released by HeLa cells was higher compared to MRC-5 fibroblasts after the incubation with 100 μg/mL. Both derivatives induced the decrease of catalase activity and glutathione levels in cancer cells without targeting the same effect in non-tumoral cells. Furthermore, the Western blot showed an increased protein expression of HSP70 and a decreased expression of HSP60 and MCM2 in cells incubated with D2 compared to control cells. We noticed differences regarding the intensity of cell death between the tested derivatives, suggesting that the modified structure after synthesis can modulate their function, the most prominent effect being observed for sample D2. In conclusion, the outcomes of our in vitro study revealed that these microwave-engineered curcumin derivatives targeted tumor cells, much more specifically, inducing their death.

This study investigated the interaction between cannabidiol (CBD) derivatives and the GPR55 receptor using a bioinformatics-driven molecular docking approach. GPR55, implicated in central nervous system (CNS) pathologies, represents a promising target for novel therapeutics. Drug-likeness evaluation via SwissADME confirmed that all selected derivatives complied with Lipinski′s Rule of Five, exhibiting favorable physicochemical properties with molecular weights below 500 Da and acceptable logP values. Molecular docking simulations, performed using AutoDock Vina through PyRx, revealed strong binding affinities, with docking scores ranging from −9.2 to −7.2 kcal/mol, indicating thermodynamically feasible interactions. Visualization and interaction analysis identified a conserved binding pocket involving key residues, including TYR101, PHE102, TYR106, ILE156, PHE169, MET172, TRP177, PRO184, LEU185, LEU270 and MET274. Ligand clustering in this region further supports the presence of a structurally defined binding site. Molecular dynamics simulations of GPR55 in complex with the three top-scoring ligands (3″-HOCBD, THC, and CBL) revealed that all ligands remained stably bound within the cavity over 100 ns, with ligand-specific rearrangements. Predicted oral bioavailability was moderate (0.55), consistent with the need for optimized formulations to enhance systemic absorption. These findings suggest that CBD derivatives may act as potential modulators of GPR55, offering a basis for the development of novel CNS-targeted therapeutics.

The study investigated the impact of three prevalent polyphenols—quercetin, ferulic acid, and caffeic acid—on catalase activity. It was determined that all three polyphenols are capable of binding to catalase, resulting in the formation of a stable complex. This finding was corroborated through fluorescence quenching studies and kinetic modeling. At low concentrations, each polyphenol exhibited an activation effect on catalase; however, at concentrations exceeding 100 μM, they began to function as inhibitors. Notably, caffeic acid and ferulic acid were observed to protect the enzyme from operational inactivation, whereas quercetin did not demonstrate this protective effect. The association constants derived from kinetic modeling were compared with those obtained from docking simulations. The results suggest that polyphenols may exert both beneficial and potentially detrimental effects on cellular antioxidant systems, contingent upon their concentration and specific molecular interactions. This highlights the necessity for careful consideration of dosage in any prospective therapeutic applications.