Ebru Didem Kuran

Aim: The present study aims to identify the synthesis and structural characterization of acyl hydrazone- sulfonamide-containing compounds that were tested in vitro on human carbonic anhydrase (hCA) isoforms I, II, IX, and XII. Methods: Herein, acyl hydrazone derivatives containing the primary sulfonamide moiety were synthesized via a three-step synthetic pathway starting from the commercially available 4-sulfamoyl benzoic acid. Structural characterizations of the final compounds were assessed through IR IR, 1H-NMR, 13C-NMR, and elemental analyses. The in vitro profiling activity of the final compounds on the Carbonic Anhydrases (CAs; EC 4.2.1.1) I, II, IX, and XII were performed by means of the stopped-flow technique and revealed nanomolar inhibitory potencies on the selected targets. Molecular docking and molecular dynamic simulations afforded a detailed understanding of the binding modes of the most effective compounds. Results: We reported the synthesis and structural characterization of 25 acyl hydrazone-sulfonamide-containing compounds that were tested in vitro on the hCAs I, II, IX, and XII isoforms for their inhibitory features. Overall, all compounds showed nanomolar inhibition potencies on the panel of hCAs considered, and their binding modes were deciphered by means of in-silico studies. Molecular docking followed by MD simulations confirmed the stability of 4l-hCA I, 4n-hCA II, 4t-hCA II, 4v-hCA XII, and 4w-hCA XII complexes. Conclusion: This study presents a deep understanding of the structural determinants influencing the affinity and selectivity of the designed compounds towards different hCAs, thus offering valuable insights for further optimization and development in the field.

This study focused on synthesizing and characterizing novel thiosemicarbazide derivatives containing a 1,2,4-triazole moiety and evaluating their antimicrobial activity against several bacterial strains. The research aimed to identify key structural features that enhance antimicrobial efficacy through structure-activity relationship analysis and identify the minimum inhibitory concentration (MIC) of the most potent compounds to assess their potential for further development as antimicrobial agents. Nine novel thiosemicarbazide derivatives containing a 1,2,4-triazole moiety were synthesized by reacting 1,2,4-triazole derivatives with thiosemicarbazide precursors, and the products were characterized using infrared spectroscopy, proton nuclear magnetic resonance (¹H-NMR), carbon-13 nuclear magnetic resonance (¹³C-NMR) spectroscopy, and elemental analysis. The antimicrobial activity of these compounds (5a-i) was tested against Klebsiella pneumoniae (K. pneumoniae),Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, and Pseudomonas aeruginosa (P. aeruginosa), using microdilution, disk diffusion, and broth microdilution methods. Dimethyl sulfoxide was used as a negative control, and Vancomycin and Meropenem were used as positive controls, with all results converted to µM for consistent analysis. The synthesized thiosemicarbazide derivatives (5a-i) were confirmed to be structurally correct through Fourier-transform infrared spectroscopy, ¹H-NMR, and ¹³C-NMR spectroscopy. Among the tested compounds, 5e (4-bromophenyl) and 5g (n-propyl) showed significant antimicrobial activity, with 5g exhibiting the strongest effects against S. aureus and P. aeruginosa. Other derivatives, such as 5b (4-NO₂Ph), 5c (4-FPh), and 5d (4-ClPh), showed moderate activity, while no significant activity was observed against K. pneumoniae or E. faecalis. The study successfully synthesized a series of novel thiosemicarbazide derivatives with a 1,2,4-triazole moiety and evaluated their antimicrobial potential. Compounds 5e and 5g exhibited significant antibacterial activity, particularly against S. aureus and P. aeruginosa, with MIC values in the low micromolar range. These findings suggest that the compounds hold promise as potential antimicrobial agents, and further studies should focus on optimizing their efficacy and exploring their mechanism of action.

This study presents the synthesis of various non‐sulfonamide acyl hydrazone derivatives intended as multi‐target ligands for the treatment of Alzheimer's disease. The derivatives were thoroughly characterized using advanced spectroscopic techniques and their inhibitory activities against key enzymes, acetylcholinesterase (AChE) and human carbonic anhydrase I/II (hCA) were systematically assessed. The synthesized compounds demonstrated significant suppression of hCAs. The 4‐methoxycarbonyl compound ( 2a , Ki = 69.74 nM) exhibited a robust inhibitory effect against hCA I compared to the reference medication acetazolamide (AAZ, Ki = 373.46 nM). The 4‐dimethylamino compound ( 2b , K _i of 120.36 nM) exhibited superior potency compared to AAZ (K _i of 350.66 nM) against hCA II. 2,4‐dinitrobenzylidene ( 2n , K _i of 69.18 nM) derivative displayed a remarkable inhibitory effect against AChE compared to tacrine (THA, K _i of 205.78 nM). Additionally, in silico studies provided insight into the binding interactions enhancing the understanding of their multi‐target potential. This study identified compounds with varying affinities for hCA isoenzymes highlighting their potential as effective and selective hCA inhibitors. The reported compounds exhibited significant biological inhibitory potency indicating their potential as a promising lead compound against hCAs and AChE.

This study describes the synthesis and characterization of a series of novel hydrazide‐hydrazone derivatives containing a 1,2,4‐triazole ring. The compounds were characterized using various spectroscopic techniques, such as FT‐IR, ¹H‐NMR, ¹³C‐NMR, HRMS, and elemental analysis. The antiproliferative activity of the synthesized compounds was evaluated against a panel of human cancer cell lines (HCT‐116, HepG‐2, KLN205, LTPA, U138, and SW620) and healthy cell lines (HSkMC and iPSCs). Among the compounds tested, compounds 4, 5p, 5r, and 5s showed the highest effectiveness in inhibiting the growth of cancer cells with Bcl‐xL inhibitory concentration (IC₅₀) values. These compounds further demonstrated selective cytotoxicity against the Bcl‐xL‐dependent lymphoma cell line (DBs). Molecular docking studies were also performed to investigate the potential binding interactions of compounds 4, 5p, 5r, and 5s with the active site of Bcl‐xL (PDB ID: 7LH7, 1.4 Å). Mechanistic studies revealed that compounds 4, 5r, and 5s induced apoptosis predominantly through the intrinsic mitochondrial pathway, while compound 5p exhibited a distinct cell cycle arrest profile, impacting both the S and G2/M phases. Western blot analysis suggested that these compounds may downregulate cyclin expression, thereby blocking its association with Bcl‐xL. Overall, these results demonstrate the potential of these novel hydrazide‐hydrazone derivatives as anticancer agents with activity comparable or superior to doxorubicin and 5‐fluorouracil.