Alshaye Najla A, Alharbi Nuha Salamah, El-Atawy Mohamed A, El-Zawawy Reham O, Hamed Ezzat A, Elhag Mohammed, Ahmed Hoda A, Omar Alaa Z
Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia.
Chemistry Department, College of Science, Taibah University, Medina 30002, Saudi Arabia.
Heliyon. 2024 Jul 14;10(14):e34540. doi: 10.1016/j.heliyon.2024.e34540. eCollection 2024 Jul 30.
Peptic ulcer disease (PUD), often caused by infection, is a prevalent gastrointestinal condition characterized by the erosion of the gastric or duodenal mucosal lining. adheres to gastric epithelial cells, secreting toxins and disrupting the stomach's defenses. 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 were synthesized 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 -tolyl derivative exhibited the highest thermal stability while the -bromophenyl derivative showed the lowest stability but highest chemical reactivity. The HOMO-LUMO energy gaps as well as the dipole moments decreased in the order: > > , reflecting a similar reactivity trend. Molecular docking showed ligands bound effectively to the 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 anti-adhesion properties make these novel chalcones promising PUD therapeutic candidates.
消化性溃疡病（PUD）通常由感染引起，是一种常见的胃肠道疾病，其特征是胃或十二指肠黏膜层受到侵蚀。（某种物质）附着于胃上皮细胞，分泌毒素并破坏胃的防御机制。（该物质）依靠多种受体来建立感染，使得这些分子成为有吸引力的治疗靶点。本研究旨在通过结合苯并噻唑、吡唑啉和查尔酮药效基团来开发新型抗溃疡化合物。通过克莱森 - 施密特缩合反应合成了一系列查尔酮衍生物，并使用FT - IR、NMR和元素分析等光谱技术对其进行了表征。使用B3LYP方法和6 - 311G基组进行的密度泛函理论（DFT）计算表明，对甲苯基衍生物表现出最高的热稳定性，而对溴苯基衍生物显示出最低的稳定性但最高的化学反应性。最高占据分子轨道（HOMO） - 最低未占据分子轨道（LUMO）的能隙以及偶极矩按顺序递减：（某种顺序关系），反映出相似的反应活性趋势。分子对接显示配体与脲酶有效结合，对接分数在 - 5.3862至 - 5.7367千卡/摩尔之间，与兰索拉唑相比具有更高的亲和力。关键相互作用包括与活性位点残基ASN666、SER714和ASN810形成距离在3.46 - 4.34 Å之间的氢键和疏水π - 氢键。这些新型查尔酮具有的抗炎、抗菌和抗黏附特性使其成为有前景的消化性溃疡病治疗候选药物。
