Aromatic hydrazones of 7-hydrazino-8-hydroxyquinoline were studied as anti-HIV and antibacterial compounds. A set of the compounds with different aromatic moieties bearing electron-donating and electron-withdrawing substituents has been selected and obtained via the hydrazo coupling and “one-pot” click reaction with aldehydes. The compounds possess activity against both bacterial and fungal targets. Cellular Ku70-inhibiting activity has been found for the series, opening a new class of inhibitors for potential anti-HIV treatment. The compounds display anti-HIV activity in infected cells at submicromolar concentrations. Their low solubility can be overcome by incorporation in water-soluble neutral polyalginate microgels (33% wt load of the compound).

Background: Lyases are used in a wide scope of applications, making them invaluable tools in both industrial biotechnology and molecular biology. Many examples of lyases belong to the extensive family of pyridoxal 5′-phosphate (PLP)-dependent enzymes, which catalyze numerous reactions involved in amino acid metabolism, like tryptophan indole-lyase (Trpase or Tnase), tyrosine phenol-lyase (TPL), and methionine γ-lyase (MGL). Beyond their role in physiological processes, these lyases can also facilitate the synthesis of other biologically active products from non-canonical substrates. Objectives: Up till now there were only two C–S lyases known for the thiosulfinates’ biosynthesis from S-substituted L-cysteine sulfoxides—alliinase and MGL. Our study reveals for the first time that C–C lyases are capable of C–S lyase activity in reactions with S-alkyl, S-allyl and S-benzyl cysteine sulfoxides. Methods: We have compared the kinetic profiles of S-substituted L-cysteine sulfoxide degradation mediated by carbon–sulfur lyase MGL versus carbon–carbon lyases TPL and Trpase. Results: Among other S-alkyl-L-cysteine sulfoxides, petiveriin (S-benzyl-L-cysteine sulfoxide) was proven to be a substrate for all three enzymes. The potential utility of these enzymes in thiosulfinate production was supported by in vitro testing of enzyme-generated thiosulfinates against clinically relevant pathogens such as Candida albicans, Pseudomonas aeruginosa, and Staphylococcus aureus. Conclusions: Both C–S and C–C lyases—MGL, TPL, and Trpase—can be implemented for practical application in thiosulfinate synthesis.

A stereodivergent route to substituted pyrrolidine core via Lewis acid catalyzed [3+2]-cycloaddition of donor-acceptor cyclopropanes (DAC) to isoxazolines was developed. Exclusive cis-2,5-stereoselectivity was governed by kinetically-controlled conditions using Sn(OTf)2 as the catalyst, while excellent trans-2,5-stereoselectivity was achieved by thermodynamically-controlled conditions using Sc(OTf)3 as the catalyst. For the DAC bearing electron-poor substituents, Yb(NTf2)3 as the catalyst proved to be efficient due to higher Lewis acidity compared to triflates. The isoxazoline [3+2]-cycloaddition reaction was also extended to bicyclo[1.1.0]butanes (BCB), providing easy access to the 2-azabicyclo[2.1.1]hexane core that may be considered a promising 3D-bioisosteric replacement for pyrrole and pyrrolidine motifs.

Heterometallic complexes offer a promising anticancer strategy owing to their simultaneous action on multiple biological targets. In this work, we report the synthesis and evaluation of the antitumor potential of two heterometallic pyrazolate-bridged complexes, [PdCo(phen)(µ-dmpz)₂(OOCMe)₂] (PdCo) and [PdCu(phen)(µ-dmpz)₂(OOCMe)₂] (PdCu) (phen = 1,10-phenanthroline, dmpz = 3,5-dimethylpyrazole). The complexes were comprehensively characterized using a combined spectroscopic and analytical approach, including single-crystal X-ray diffraction (SC-XRD), PXRD, FTIR, UV-Vis, and mass spectrometry, confirming their structural integrity in both solid state and solution. Their cytotoxicity was assessed in vitro against colon, A549 lung, and breast cancer cell lines, as well as normal human dermal fibroblasts. The complexes exhibited micromolar IC₅₀ values with selectivity indices up to 7. Using circular dichroism (CD) and fluorescence spectroscopy, it was demonstrated that PdCo binds to DNA, with minor groove binding (K_d = 7.6 μM) being the preferred mode of interaction, dominating over intercalation (K_d = 26.1 μM). Molecular docking simulations confirmed that the dissociated [Pd(phen)(µ-dmpz)₂] fragment is capable of binding to DNA. Furthermore, chemiluminescence assays revealed pronounced peroxidase-like and superoxide dismutase-like activities of PdCu and PdCo, implicating ROS-mediated oxidative stress as a second, complementary cytotoxic pathway. Collectively, these findings highlight the dual-action mechanism of the synthesized complexes, combining DNA targeting with ROS-mediated oxidative damage, positioning them as highly potent candidates for further anticancer development.