Khan Shoaib, Iqbal Tayyiaba, Rehman Mujaddad Ur, Khan Muhammad Bilal, Islam Mohammad Shahidul, Dahlous Kholood A
Department of Chemistry, Abbottabad University of Science and Technology, Abbottabad, 22500 Pakistan.
Department of Microbiology, Abbottabad University of Science and Technology, Abbottabad, 22500 Pakistan.
3 Biotech. 2025 Jun;15(6):176. doi: 10.1007/s13205-025-04313-6. Epub 2025 May 17.
In the current study, a novel route was established for the synthesis of hybrid benzothiazole derived thiazole bearing -thiazolidinone-chalcone (1-15) scaffolds. These compounds were screened for their biological potential as anti-Alzheimer therapeutic agents by inhibiting acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. The biological evaluation and molecular docking studies revealed that most of the synthesized compounds exhibited significant inhibitory activity against both enzymes, outperforming the standard drug, donepezil. Among them, Analog 15 demonstrated remarkable therapeutic potential, with IC₅₀ values of 3.30 ± 0.70 µM and 3.80 ± 0.90 µM, as well as strong binding affinities/docking scores of - 8.97 and - 12.84 kcal/mol for AChE and BuChE, respectively. Additionally, enzyme kinetics analysis using Lineweaver-Burk plots confirmed the mode of inhibition of the synthesized analogs. Pharmacokinetic predictions further supported the drug-like properties of these compounds, highlighting favorable pharmacological profiles, including good water solubility, non-carcinogenicity, and biological safety. The findings presented in this study provide compelling evidence for the anti-Alzheimer potential of these novel scaffolds, warranting further investigation through in vivo studies and clinical exploration to assess their full therapeutic applicability.
The online version contains supplementary material available at 10.1007/s13205-025-04313-6.
在当前的研究中，建立了一种合成含噻唑烷酮-查尔酮（1-15）支架的杂化苯并噻唑衍生噻唑的新途径。通过抑制乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE），对这些化合物作为抗阿尔茨海默病治疗剂的生物潜力进行了筛选。生物学评价和分子对接研究表明，大多数合成化合物对这两种酶均表现出显著的抑制活性，优于标准药物多奈哌齐。其中，类似物15表现出显著的治疗潜力，对AChE和BuChE的IC₅₀值分别为3.30±0.7µM和3.80±0.9µM，结合亲和力/对接分数分别为-8.97和-12.84kcal/mol。此外，使用Lineweaver-Burk图进行的酶动力学分析证实了合成类似物的抑制模式。药代动力学预测进一步支持了这些化合物的类药物性质，突出了良好的药理学特性，包括良好的水溶性、非致癌性和生物安全性。本研究结果为这些新型支架的抗阿尔茨海默病潜力提供了有力证据，有必要通过体内研究和临床探索进行进一步研究，以评估其完全的治疗适用性。
在线版本包含可在10.1007/s13205-025-04313-6获取的补充材料。
