Piperonal-derived Schiff base molecules as potential multi-target therapeutic agents against Alzheimer's and diabetes.

IF 3.4 4区医学 Q3 CHEMISTRY, MEDICINAL

Future medicinal chemistry Pub Date : 2025-08-01 Epub Date: 2025-08-30 DOI:10.1080/17568919.2025.2549677

Asif Ahmad, Uzma Salar, Musa Özil, Nimet Baltaş, Syeda Sumayya Tariq, Zaheer Ul-Haq, Khalid Mohammed Khan, Farzana Shaheen

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引用次数: 0

Abstract

Background: The dual burden of diabetes and Alzheimer's highlights the urgent need for multifunctional therapeutic agents. This study explores piperonal-derived Schiff base derivatives as potential dual-action enzyme inhibitors against α-amylase (AA), α-glucosidase (AG), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), offers a promising strategy for managing both conditions.

Methods: Schiff base derivatives of piperonal (heliotropin) were synthesized, structurally characterized, and explored against established drug targets of diabetes mellitus (DM) and Alzheimer's disease (AD).

Results: Compounds 7 (IC₅₀ = 5.73 ± 0.01; 3.52 ± 0.02 µM) and 17 (IC₅₀ = 10.91 ± 0.02; 7.38 ± 0.02 µM) showed potent inhibitory effects against AG and AA enzymes, in comparison to acarbose (IC₅₀ = 14.98 ± 0.02 µM; 14.64 ± 0.02 µM). However, analogs 7, 9, 10, 14, and 15, compounds 7 (IC₅₀ = 2.92 ± 0.02; 3.34 ± 0.02 µM) and 9 (IC₅₀ = 8.16 ± 0.03; 7.19 ± 0.03 µM) showed remarkable inhibitory results against AChE and BChE, respectively, compared to standard donepezil chloride (IC₅₀ = 37.89 ± 0.02 µM; 41.56 ± 0.03 µM). Comprehensive kinetic analyses and molecular docking supported findings by in vitro studies. Synthesized derivatives were also checked for their antioxidant potential and demonstrated significant activity.

Conclusion: These complementary studies highlight several hit candidates for further development as therapeutic agents against DM and AD.

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胡椒醛衍生的希夫碱分子作为治疗阿尔茨海默病和糖尿病的潜在多靶点药物。

背景：糖尿病和阿尔茨海默病的双重负担突出了对多功能治疗药物的迫切需求。本研究探讨了胡椒醛衍生的希夫碱衍生物作为α-淀粉酶（AA）、α-葡萄糖苷酶（AG）、乙酰胆碱酯酶（AChE）和丁基胆碱酯酶（BChE）的潜在双作用酶抑制剂，为管理这两种疾病提供了一种有前途的策略。方法：合成胡椒碱衍生物（heliotropin），对其进行结构表征，并对糖尿病（DM）和阿尔茨海默病（AD）的既定药物靶点进行探索。结果：化合物7 （IC50 = 5.73±0.01;3.52±0.02µM）和化合物17 （IC50 = 10.91±0.02;7.38±0.02µM）与阿卡波糖（IC50 = 14.98±0.02µM; 14.64±0.02µM）相比，对AG和AA酶具有较强的抑制作用。然而，类似物7、9、10、14和15，化合物7 （IC50 = 2.92±0.02;3.34±0.02µM）和9 （IC50 = 8.16±0.03;7.19±0.03µM）对AChE和BChE的抑制效果明显优于标准氯多奈哌齐（IC50 = 37.89±0.02µM; 41.56±0.03µM）。综合动力学分析和分子对接支持了体外研究的发现。合成的衍生物也被检查了它们的抗氧化潜力，并显示出显著的活性。结论：这些互补性研究突出了一些候选药物，作为进一步开发治疗糖尿病和阿尔茨海默病的药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Future medicinal chemistry CHEMISTRY, MEDICINAL-

CiteScore

5.80

自引率

2.40%

发文量

118

审稿时长

4-8 weeks

期刊介绍： Future Medicinal Chemistry offers a forum for the rapid publication of original research and critical reviews of the latest milestones in the field. Strong emphasis is placed on ensuring that the journal stimulates awareness of issues that are anticipated to play an increasingly central role in influencing the future direction of pharmaceutical chemistry. Where relevant, contributions are also actively encouraged on areas as diverse as biotechnology, enzymology, green chemistry, genomics, immunology, materials science, neglected diseases and orphan drugs, pharmacogenomics, proteomics and toxicology.