Department of Chemistry, Government College University, Faisalabad, Pakistan.
Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan.
Pak J Pharm Sci. 2021 Sep;34(5(Supplementary)):1909-1915.
α-Glucosidase inhibitors occupy a prominent position among the various treatments of type-2 diabetes mellitus (DM2). In this study, a series of new norfloxacin-acetanilide hybrid molecules were synthesized and screened for α-glucosidase inhibition activity. The synthetic methodology involves the synthesis of a series of α-bromoacetanilides by condensing bromoacetyl bromide with various substituted anilines. These α-bromoacetanilides were coupled with norfloxacin in DMF to get the titled hybrids. The structure elucidation of synthesized compounds were characterized by H NMR, C NMR and LC-MS. Finally, the compounds were screened for their α-glucosidase inhibition activity using acarbose as a reference drug (IC =58 μM). Among the tested compounds, 3i and 3j displayed potent α-glucosidase inhibition activity with IC values of 7.81±0.038 and 5.55±0.012 μM respectively. In-addition, 3m, 3f and 3k were demonstrated moderate alpha-glucosidase inhibition activities with IC values of 52.905±0.041, 23.79± 0.087 and 23.06±0.026 μM respectively. The structure-activity relationship was established with the help of molecular docking by using Molecular Operating Environment software (MOE 2014).
α-葡萄糖苷酶抑制剂在 2 型糖尿病（DM2）的各种治疗方法中占据重要地位。在这项研究中，合成了一系列新的诺氟沙星-乙酰苯胺类杂合分子，并对其α-葡萄糖苷酶抑制活性进行了筛选。该合成方法涉及通过溴乙酰溴与各种取代苯胺缩合合成一系列α-溴代乙酰苯胺。将这些α-溴代乙酰苯胺在 DMF 中与诺氟沙星偶联得到标题杂合分子。通过 1H NMR、13C NMR 和 LC-MS 对合成化合物的结构进行了阐明。最后，使用阿卡波糖作为参考药物（IC=58 μM）对化合物进行了α-葡萄糖苷酶抑制活性筛选。在所测试的化合物中，化合物 3i 和 3j 表现出较强的α-葡萄糖苷酶抑制活性，IC 值分别为 7.81±0.038 和 5.55±0.012 μM。此外，化合物 3m、3f 和 3k 表现出适度的α-葡萄糖苷酶抑制活性，IC 值分别为 52.905±0.041、23.79±0.087 和 23.06±0.026 μM。通过使用 Molecular Operating Environment 软件（MOE 2014）进行分子对接，建立了构效关系。
