Ahmed Javed, Khan Mohsin Abbas, Khaliq Saharish, Masood Anum, Bhat Mashooq A, Khan Muhammad Rizwan, Raza Asim, Al-Omar Mohamed A, Ullah Farhat
Department of Pharmaceutical Chemistry, The Islamia University of Bahawalpur Pakistan, Bahawalpur, Pakistan.
Institute of Pharmaceutical Science, Faculty of Life Science and Medicine, King's College, London, UK.
Future Med Chem. 2025 Jan;17(2):195-207. doi: 10.1080/17568919.2024.2447223. Epub 2024 Dec 31.
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.
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.
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.
本研究聚焦于新型西他列汀衍生物的合成与表征，旨在开发出强效、口服活性且副作用最小的抗糖尿病药物，用于治疗2型糖尿病。通过模板反应合成了基于西他列汀的衍生物的铜（II）（SCu1 - SCu9）和锌（II）（SZn1 - SZn9）金属配合物。
使用元素分析、傅里叶变换红外光谱（FTIR）、紫外可见光谱（UV - Vis）、1H核磁共振（1h NMR）和13C核磁共振光谱对合成的配合物进行全面表征。通过α -淀粉酶和α -葡萄糖苷酶抑制试验评估这些化合物的生物功效，分子模拟研究进一步证实了它们的抑制活性。
在测试的衍生物中，SD7、SD4、SD3、SD5和SD9表现出与标准抑制剂相当的酶抑制谱。然而，金属配合物存在吸收方面的问题，这可能会影响它们的生物利用度。
这些发现突出了合成化合物对靶向酶具有显著的抗糖尿病潜力，为其在未来治疗研究中作为先导分子的开发奠定了基础。
