Khan Shoaib, Iqbal Tayyiaba, Hussain Rafaqat, Khan Yousaf, Fiaz Zanib, Rahim Fazal, Darwish Hany W
Department of Chemistry, Abbottabad University of Science and Technology (AUST), Abbottabad 22500, Pakistan.
College of Biology, Hunan University, Changsha 410082, China.
Pharmaceuticals (Basel). 2024 Oct 24;17(11):1428. doi: 10.3390/ph17111428.
To synthesize hybrid compounds of indole and oxadiazole in search of highly effective anti-diabetic therapeutic agent. With the goal of advancing diabetes research, our group designed and synthesized a library of 15 compounds based on indole-derived oxadiazole bearing varied substituted thiazolidinone via a multistep synthetic route. C-NMR, H-NMR and HREI-MS were applied for the characterization of all the synthesized compounds. Their biological inhibitory activity against diabetic enzymes, i.e., α-amylase and α-glucosidase was also determined. Compound excellent inhibition against α-amylase and α-glucosidase than the standard acarbose (IC = 8.50 ± 0.10 µM for α-amylase and 9.30 ± 0.30 µM for α-glucosidase. To ensure the inhibitory actions of these potent analogs in molecular docking, an in silico approach was used. To determine the drug likeness of the reported analogs, an ADMET investigation was also carried out to explore the nature of the designed compounds if used as a drug. Fluoro-substituted analog 15 has stronger inhibition profile against both enzymes. All the potent compounds can be used as effective anti-diabetic therapeutic agents in future.
为了合成吲哚和恶二唑的杂化化合物以寻找高效抗糖尿病治疗剂。为了推进糖尿病研究，我们的团队通过多步合成路线设计并合成了一个基于吲哚衍生的恶二唑并带有不同取代噻唑烷酮的15种化合物的文库。采用碳核磁共振、氢核磁共振和高分辨电子轰击质谱对所有合成化合物进行表征。还测定了它们对糖尿病相关酶即α-淀粉酶和α-葡萄糖苷酶的生物抑制活性。化合物对α-淀粉酶和α-葡萄糖苷酶的抑制作用优于标准阿卡波糖（α-淀粉酶的半数抑制浓度为8.50±0.10μM，α-葡萄糖苷酶的半数抑制浓度为9.30±0.30μM）。为了确保这些强效类似物在分子对接中的抑制作用，采用了计算机模拟方法。为了确定所报道类似物的药物相似性，还进行了药物代谢及药物动力学研究以探索这些设计化合物用作药物时的性质。氟取代类似物15对这两种酶具有更强的抑制作用。所有强效化合物未来都可作为有效的抗糖尿病治疗剂。
