Synthesis, DFT, and in silico biological evaluation of chalcone bearing pyrazoline ring against Helicobacter pylori receptors.
| Autor: | Alshaye NA; Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia., Alharbi NS; Chemistry Department, College of Science, Taibah University, Medina 30002, Saudi Arabia., El-Atawy MA; Chemistry Department, Faculty of Science, Alexandria University, Alexandria, 21231, Egypt., El-Zawawy RO; Chemistry Department, Faculty of Science, Alexandria University, Alexandria, 21231, Egypt., Hamed EA; Chemistry Department, Faculty of Science, Alexandria University, Alexandria, 21231, Egypt., Elhag M; Chemistry Department, Faculty of Science, Damanhour University, Damanhour, 22511, Egypt., Ahmed HA; Department of Chemistry, Faculty of Science, Cairo University, Giza, 12613, Egypt., Omar AZ; Chemistry Department, Faculty of Science, Damanhour University, Damanhour, 22511, Egypt. |
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| Jazyk: | angličtina |
| Zdroj: | Heliyon [Heliyon] 2024 Jul 14; Vol. 10 (14), pp. e34540. Date of Electronic Publication: 2024 Jul 14 (Print Publication: 2024). |
| DOI: | 10.1016/j.heliyon.2024.e34540 |
| Abstrakt: | Peptic ulcer disease (PUD), often caused by Helicobacter pylori infection, is a prevalent gastrointestinal condition characterized by the erosion of the gastric or duodenal mucosal lining. H. pylori adheres to gastric epithelial cells, secreting toxins and disrupting the stomach's defenses. H. pylori relies on various receptors to establish infection, making these molecules attractive therapeutic targets. This study aimed to develop novel anti-ulcer compounds by combining benzothiazole, pyrazoline, and chalcone pharmacophores. A series of chalcone derivatives 4a-c were synthesized via Claisen-Schmidt condensation and characterized using spectroscopic techniques such as FT-IR, NMR and elemental analysis. The DFT calculations, using B3LYP method with 6-311G basis set, revealed the p -tolyl derivative 4b exhibited the highest thermal stability while the p -bromophenyl derivative 4c showed the lowest stability but highest chemical reactivity. The HOMO-LUMO energy gaps as well as the dipole moments decreased in the order: 4b > 4a > 4c , reflecting a similar reactivity trend. Molecular docking showed ligands 4a-c bound effectively to the H. pylori urease enzyme, with docking scores from -5.3862 to -5.7367 kcal/mol with superior affinity over lansoprazole. Key interactions involved hydrogen bonds and hydrophobic pi-hydrogen bonds with distances ranging 3.46-4.34 Å with active site residues ASN666, SER714 and ASN810. The combined anti-inflammatory, antimicrobial, and H. pylori anti-adhesion properties make these novel chalcones promising PUD therapeutic candidates. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 The Authors.) |
| Databáze: | MEDLINE |
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