Various novel barbituric and thiobarbituric acid derived sulphonamides were synthesized in excellent yield via three components single pot reaction; and these were screened for in vitro urease inhibition studies against jack bean urease. The compounds 1‐7 were found to exhibit a low to moderate activity whereas compounds 8‐14 showed a significant activity (88.3‐99.9% inhibition determined at 500 μM concentration). Structures of the synthesized compounds were confirmed by ¹H‐NMR, ¹³C‐NMR, mass spectrometry and elemental analysis data.

Purpose: To design and synthesize a series of new structural motifs of urease inhibitors, 3- [{(substituted phenyl) amino} methyl]-5-(3, 4, 5-trimethoxyphenyl)-1,3,4-oxadiazole-2(3H)-thiones and 3- {[(pyridin-2-yl)amino]methyl}-5-(3,4,5-trimethoxy phenyl)-1,3,4-oxadiazole-2(3H)-thiones from 1, 3, 4- oxadiazole-2-thione. Methods: Targeted Mannich base derivatives were synthesized by the reaction of 1, 3, 4-oxadiazole-2- thione with formaldehyde and respective aromatic amines. These structural motifs were subjected to ¹H–NMR, ¹³C–NMR and mass spectrometric analysis. Compound 4, i.e., 1,3,4-oxadiazole-2-thione and its corresponding Mannich bases (5-17) were subjected to in silico screening as urease inhibitors, using crystal structure of urease (Protein Data Bank ID: 5FSE) as a model enzyme. Furthermore, the targeted compounds were evaluated for their in vitro urease inhibition and anti-oxidant activities using thiourea and propyl gallate as standards, respectively. Results: The docking score of targeted compounds predicted that they are promising urease inhibitors. Subsequently, in vitro studies on Jack bean urease supported the results from virtual screening, and found compounds 4, 5, 9,10,12, 13, 14 and 15 very potent urease inhibitors with half-maximal inhibitory concentration (IC₅₀) values in the range of 5.93 ± 0.13 to 9.76 ± 0.11, relative to thiourea (IC₅₀ = 21.25 ± 0.15). Compounds 4 – 6, and compounds 12 - 17 also exhibited higher antioxidant activities than propyl gallate. Conclusion: In view of their potent urease inhibition and antioxidant activities, these structural motifs have potentials as new candidates for the development of anti-ulcer drugs. Keywords: 1, 3, 4-Oxadiazole-2-thiones, Antioxidant, Molecular docking, Urease inhibition, Anti-ulcer

Chronic wounds pose a global challenge, often requiring the use of multifunctional materials that facilitate healing while protecting against infection. The present study develops porous, biodegradable and antibacterial composite hydrogels from chitosan and polyvinyl alcohol (PVA) incorporating honey and aloe vera gel as antimicrobial agents for healing chronic wounds. Hydrogels were prepared by freeze gelation methodology, and further crosslinked with citric acid. FTIR spectra confirmed the presence of characteristic functional groups and showed a reduction in the peak intensities of O–H, N–H, and amide bands in crosslinked hydrogels. Scanning electron micrographs illustrated the clear morphological changes; citric acid crosslinked hydrogels (GG-05, GG-06, GG-08) exhibited more porous, sponge-like structures, with GG-08 achieving the highest porosity, having an average pore size of 21.28 μm. The hydrogel GG-08 demonstrated the greatest water retention capacity, reaching up to 218%, while GG-04 showed the highest degradation of 93% ± 3. The developed hydrogels exhibited better antibacterial properties, especially GG-03, GG-04, GG-07 and GG-08 had excellent activity against Gram-positive Staphylococcus aureus (S. aureus). Similarly, GG-01 and GG-05 showed excellent activities against Gram-negative bacterial strains, i.e. Escherichia coli (E. coli) and Klebsiella pneumonia (K. pneumonia). Anti-hemolytic testing confirmed the biocompatibility and non-toxic nature of hydrogels. The results demonstrated that citric acid addition has significantly improved the antibacterial potential against E. coli and K. pneumonia and also enhanced solution absorption, water retention and moisture content. Overall, these hydrogels demonstrated potential as advanced wound dressings, owing to their better moisture retention, broad-spectrum antibacterial properties and excellent biocompatibility.