Ajaz Aliya, Shaheen Muhammad Ashraf, Fayyaz Ur Rehman Muhammad, Ahmad Maqsood, Munawar Khurram Shahzad, Siddique Abu Bakar, Ashfaq Muhammad, Ahmad Nazir
Institute of Chemistry, University of Sargodha 40100 Pakistan
Department of Allied Health Sciences, Superior University Sargodha-Campus 40100 Pakistan.
RSC Adv. 2025 Jun 4;15(23):18752-18765. doi: 10.1039/d5ra00065c. eCollection 2025 May 29.
Diabetes mellitus is a significant health issue in Pakistan, with rising prevalence rates posing serious challenges to public health. To tackle this issue, several strategies have been developed recently, among which the controlled conversion of dietary carbohydrates into glucose by inhibition of enzymes is an appropriate strategy. For this purpose, many synthetic drugs have been tried and explored. In this scenario, a new Schiff base ligand, ()-2-((adamantan-2-ylimino)methyl)-6-bromo-4-chlorophenol (AHB), has been synthesized by a reflux reaction of amantadine with 3-bromo-5-chloro-2-hydroxybenzaldehyde. The transition metal complexes, [Cr(AHB)], [Zn(AHB)], [Co(AHB)], and [VO(AHB)], were also synthesized by reacting AHB with the respective metal salts. Structural elucidation of the prepared compounds was performed comprehensively by various physicochemical methods like UV-visible, H and C-NMR, FT-IR, mass spectrometry, elemental analysis, thermal analysis, and molar conductivity. Structural investigation of crystalline AHB was also performed by single-crystal X-ray crystallography. Based on the structural analysis, an octahedral geometry for the Cr(iii) complex, square planar geometry for the Co(ii) complex, tetrahedral geometry for the Zn(ii) complex, and square pyramidal geometry for the VO(iv) complex were proposed. The synthesized bidentate ligand was found to be coordinated with the metal ions nitrogen and oxygen donor atoms. All of the synthesized compounds were found to be non-electrolytic. The thermogravimetric analysis demonstrated the thermally stable nature of complexes, more than the ligand. The hypoglycemic potential of the compounds was estimated by inhibitory activities of α-amylase and α-glucosidase enzymes. The tested ligand-AHB was found to be relatively inactive toward both enzymes, while its metal complexes were found to be good α-glucosidase inhibitors as compared to α-amylase inhibitors. Among all prepared compounds, the Zn(ii) complex was found to be a good α-glucosidase inhibitor comparable to the standard (acarbose), while other complexes showed a moderate inhibition of α-glucosidase. Both Cr(iii) and Co(ii) complexes were found to be effective α-amylase inhibitors. Based on the current findings, it can be anticipated that the synthesized compounds can be tried as effective therapeutic agents to cure diabetes mellitus.
糖尿病在巴基斯坦是一个重大的健康问题，患病率不断上升给公共卫生带来了严峻挑战。为应对这一问题，最近已制定了多项策略，其中通过抑制酶将膳食碳水化合物可控地转化为葡萄糖是一种合适的策略。为此，人们尝试并探索了许多合成药物。在这种情况下，一种新的席夫碱配体，即（）-2-（（金刚烷-2-基亚氨基）甲基）-6-溴-4-氯苯酚（AHB），通过金刚烷与3-溴-5-氯-2-羟基苯甲醛的回流反应合成。过渡金属配合物[Cr(AHB)]、[Zn(AHB)]、[Co(AHB)]和[VO(AHB)]也通过使AHB与相应的金属盐反应而合成。通过紫外可见光谱、氢和碳核磁共振、傅里叶变换红外光谱、质谱、元素分析、热分析和摩尔电导率等各种物理化学方法对所制备化合物进行了全面的结构解析。还通过单晶X射线晶体学对结晶态的AHB进行了结构研究。基于结构分析，提出了Cr(iii)配合物的八面体几何结构、Co(ii)配合物的平面正方形几何结构、Zn(ii)配合物的四面体几何结构以及VO(iv)配合物的正方锥几何结构。发现合成的双齿配体与金属离子通过氮和氧供体原子配位。所有合成化合物均被发现是非电解质。热重分析表明配合物的热稳定性高于配体。通过α-淀粉酶和α-葡萄糖苷酶的抑制活性评估了化合物的降血糖潜力。测试发现配体AHB对这两种酶相对无活性，而其金属配合物与α-淀粉酶抑制剂相比是良好的α-葡萄糖苷酶抑制剂。在所有制备的化合物中，发现Zn(ii)配合物是一种与标准药物（阿卡波糖）相当的良好α-葡萄糖苷酶抑制剂，而其他配合物对α-葡萄糖苷酶表现出中等程度的抑制作用。发现Cr(iii)和Co(ii)配合物都是有效的α-淀粉酶抑制剂。基于当前的研究结果，可以预期所合成的化合物可作为治疗糖尿病的有效治疗剂进行尝试。
