Synthesis, characterization, and enzyme inhibition evaluation of sitagliptin derivatives and their metal complexes.

IF 3.2 4区医学 Q3 CHEMISTRY, MEDICINAL

Future medicinal chemistry Pub Date : 2025-01-01 Epub Date: 2024-12-31 DOI:10.1080/17568919.2024.2447223

Javed Ahmed, Mohsin Abbas Khan, Saharish Khaliq, Anum Masood, Breena, Mashooq A Bhat, Muhammad Rizwan Khan, Asim Raza, Mohamed A Al-Omar, Farhat Ullah

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引用次数: 0

Abstract

Aims: This study focuses on the synthesis and characterization of novel sitagliptin derivatives, aiming to develop potent, orally active anti-diabetic agents with minimal side effects for the management of type 2 diabetes mellitus. Copper (II) (SCu1-SCu9) and zinc (II) (SZn1-SZn9) metal complexes of sitagliptin-based derivatives were synthesized via a template reaction.

Material & method: The synthesized complexes were comprehensively characterized using elemental analysis, FTIR, UV-Vis, 1 h NMR, and 13C NMR spectroscopy. The biological efficacy of these compounds was assessed through α-amylase and α-glucosidase enzyme inhibition assays, with molecular simulation studies providing additional confirmation of their inhibitory activity.

Results: Among the tested derivatives, SD7, SD4, SD3, SD5, and SD9 demonstrated enzyme inhibition profiles comparable to the standard inhibitors. However, the metal complexes exhibited absorption challenges, which may influence their bioavailability.

Conclusion: These findings highlight the significant anti-diabetic potential of the synthesized compounds against targeted enzymes, establishing a foundation for their development as lead molecules in future therapeutic research.

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西格列汀衍生物及其金属配合物的合成、表征及酶抑制评价。

目的：本研究主要研究新型西格列汀衍生物的合成和表征，旨在开发有效的、口服活性的、副作用最小的抗2型糖尿病药物。通过模板反应合成了西格列汀基衍生物的铜（II）（SCu1-SCu9）和锌（II）（SZn1-SZn9）金属配合物。材料与方法：采用元素分析、FTIR、UV-Vis、1h NMR、13C NMR等方法对合成的配合物进行了综合表征。通过α-淀粉酶和α-葡萄糖苷酶抑制实验评估了这些化合物的生物学功效，并通过分子模拟研究进一步证实了它们的抑制活性。结果：在所测试的衍生物中，SD7、SD4、SD3、SD5和SD9表现出与标准抑制剂相当的酶抑制特性。然而，金属配合物表现出吸收困难，这可能影响其生物利用度。结论：这些发现突出了合成的化合物对靶向酶具有显著的抗糖尿病潜力，为其在未来的治疗研究中作为先导分子的发展奠定了基础。

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.