Sultan Hira, Arshad Nuzhat, Lateef Mehreen
Department of Chemistry, NED University of Engineering and Technology, Karachi 75270, Pakistan.
Multidisciplinary Lab, Bahria University of Karachi, Karachi 75270, Pakistan.
Molecules. 2025 May 2;30(9):2033. doi: 10.3390/molecules30092033.
Crown ethers have gained importance in the field of medicine because of their resemblance to natural ionophores like valinomycin. With the goal of developing new pharmacologically important crown ethers, a novel series of crown ethers linked with Fusidic acid butyl ester - were synthesized and characterized by means of their H NMR, C NMR DEPT-135, FT-IR, and mass spectrometry. In vitro antioxidant and α-glucosidase inhibition activities of all crown ethers along with the precursor Fusidic acid butyl ester were examined and compared to the standard butylated hydroxyanisole and acarbose, respectively. Compounds (FABE-16-crown-4) and (FABE-19-crown-5) showed high antioxidant potential with the IC = 22.5 ± 0.2 μM and 32.1 ± 0.3 μM, respectively, when compared to the standard BHA (IC = 44.2 ± 0.34 μM). To understand the binding mode of the compounds, molecular docking investigations were performed using human antioxidant protein, peroxiredoxin 5. Molecular docking studies revealed higher docking scores (-6.5 and -6.7 kcal/mol) for the highly active compounds and , respectively, than standard BHA (-5.3 kcal/mol). Synthesized crown ethers exhibited moderate α-glucosidase inhibition with (IC = 23.5 ± 0.2 to 76.5 ± 0.1 μM) when compared to acarbose as standard (IC = 5.2 ± 0.8 μM). The in silico ADMET predictions indicated that the prepared compounds obeyed (bRO5) and Veber's rule for the acceptance as orally administered drugs and indicated that all the prepared crown ethers exhibited calculated values of drug likeness parameters in acceptable ranges that showed good potential of these molecules for further drug development investigations.
冠醚因其与缬氨霉素等天然离子载体相似而在医学领域变得重要起来。为了开发具有重要药理作用的新型冠醚，合成了一系列与夫西地酸丁酯相连的新型冠醚，并通过氢核磁共振、碳核磁共振DEPT - 135、傅里叶变换红外光谱和质谱对其进行了表征。研究并比较了所有冠醚以及前体夫西地酸丁酯的体外抗氧化和α - 葡萄糖苷酶抑制活性，分别与标准丁基化羟基茴香醚和阿卡波糖进行对比。与标准丁基化羟基茴香醚（IC = 44.2 ± 0.34 μM）相比，化合物（FABE - 16 - 冠 - 4）和（FABE - 19 - 冠 - 5）分别表现出高抗氧化潜力，IC50值分别为22.5 ± 0.2 μM和32.1 ± 0.3 μM。为了解这些化合物的结合模式，使用人类抗氧化蛋白过氧化物还原酶5进行了分子对接研究。分子对接研究表明，高活性化合物和的对接分数分别更高（-6.5和-6.7 kcal/mol），高于标准丁基化羟基茴香醚（-5.3 kcal/mol）。与作为标准的阿卡波糖（IC50 = 5.2 ± 0.8 μM）相比，合成的冠醚表现出中等程度的α - 葡萄糖苷酶抑制作用（IC50 = 23.5 ± 0.2至76.5 ± 0.1 μM）。计算机辅助的ADMET预测表明，所制备的化合物符合作为口服给药药物的（bRO5）和维贝尔规则，并且表明所有制备的冠醚的药物相似性参数计算值在可接受范围内，显示出这些分子在进一步药物开发研究中的良好潜力。
