PDF(Pubmed)
Abstract：
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.
摘要：
消化性溃疡病(PUD),通常由幽门螺杆菌感染引起，是一种常见的胃肠道疾病，其特征是胃或十二指肠粘膜衬里的侵蚀。幽门螺杆菌粘附于胃上皮细胞，分泌毒素，破坏胃的防御。幽门螺杆菌依赖于各种受体来建立感染，使这些分子成为有吸引力的治疗靶标。本研究旨在通过结合苯并噻唑开发新型抗溃疡化合物，吡唑啉,和查尔酮药效团。通过Claisen-Schmidt缩合合成了一系列查尔酮衍生物4a-c，并使用FT-IR等光谱技术进行了表征。NMR和元素分析。DFT计算，使用具有6-311G基集的B3LYP方法，揭示了对甲苯基衍生物4b表现出最高的热稳定性,而对溴苯基衍生物4c表现出最低的稳定性但最高的化学反应性。HOMO-LUMO能隙和偶极矩按以下顺序减小：4b>4a>4c，反映了类似的反应性趋势。分子对接显示配体4a-c与幽门螺杆菌脲酶有效结合，对接评分为-5.3862至-5.7367kcal/mol，亲和力优于兰索拉唑。关键相互作用涉及氢键和疏水性pi-氢键，距离范围为3.46-4.34，活性位点残基ASN666，SER714和ASN810。联合抗炎，抗菌，和H.pylori抗粘附特性使这些新型查耳酮成为有前途的PUD治疗候选物。
