Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800, Pakistan.
Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
Bioorg Chem. 2019 Mar;84:372-383. doi: 10.1016/j.bioorg.2018.11.053. Epub 2018 Nov 30.
Xanthenone based hydrazone derivatives (5a-n) have been synthesized as potential α-glucosidase inhibitors. All synthesized compounds (5a-n) are characterized by their FTIR, H NMR, C NMR and HRMS, and in case of 5g also by X-ray crystallographic technique. The compounds unveiled a varying degree of α-glucosidase inhibitory activity when compared with standard acarbose (IC = 375.38 ± 0.12 µM). Amongst the series, compound 5l (IC = 62.25 ± 0.11 µM) bearing a trifluoromethyl phenyl group is found to be the most active compound. Molecular modelling is performed to establish the binding pattern of the more active compound 5l, which revealed the significance of substitution pattern. The pharmacological properties of molecules are also calculated by MedChem Designer which determines the ADME (absorption, distribution, metabolism, excretion) properties of molecules. The solid state self-assembly of compound 5g is discussed to show the conformation and role of iminoamide moiety in the molecular packing.
基于氧杂蒽酮的腙衍生物（5a-n）已被合成，作为有潜力的α-葡萄糖苷酶抑制剂。所有合成的化合物（5a-n）都通过傅里叶变换红外光谱（FTIR）、核磁共振氢谱（1H NMR）、核磁共振碳谱（13C NMR）和高分辨质谱（HRMS）进行了表征，而 5g 化合物还通过 X 射线晶体学技术进行了表征。与标准阿卡波糖（IC = 375.38 ± 0.12 µM）相比，这些化合物表现出不同程度的α-葡萄糖苷酶抑制活性。在该系列中，含有三氟甲基苯基的化合物 5l（IC = 62.25 ± 0.11 µM）显示出最强的活性。通过分子模拟建立了更活性化合物 5l 的结合模式，揭示了取代模式的重要性。通过 MedChem Designer 计算了分子的药理学性质，确定了分子的 ADME（吸收、分布、代谢、排泄）性质。讨论了化合物 5g 的固态自组装，以展示亚胺酰胺部分在分子堆积中的构象和作用。
