Department of Biology, College of Science, Hail University, P.O. Box 2440, Hail 2440, Saudi Arabia.
Laboratory of Heterocyclic Chemistry Natural Product and Reactivity/CHPNR, Department of Chemistry, Faculty of Science of Monastir, University of Monastir, Monastir 5000, Tunisia.
Molecules. 2022 Oct 25;27(21):7248. doi: 10.3390/molecules27217248.
To combat emerging antimicrobial-resistant microbes, there is an urgent need to develop new antimicrobials with better therapeutic profiles. For this, a series of 13 new spiropyrrolidine derivatives were designed, synthesized, characterized and evaluated for their in vitro antimicrobial, antioxidant and antidiabetic potential. Antimicrobial results revealed that the designed compounds displayed good activity against clinical isolated strains, with being the most potent (MIC 3.95 mM against ATCC 25923) compared to tetracycline (MIC 576.01 mM). The antioxidant activity was assessed by trapping DPPH, ABTS and FRAP assays. The results suggest remarkable antioxidant potential of all synthesized compounds, particularly , exhibiting the strongest activity with IC of 3.26 ± 0.32 mM (DPPH), 7.03 ± 0.07 mM (ABTS) and 3.69 ± 0.72 mM (FRAP). Tested for their -amylase inhibitory effect, the examined analogues display a variable degree of -amylase activity with IC ranging between 0.55 ± 0.38 mM and 2.19 ± 0.23 mM compared to acarbose (IC 1.19 ± 0.02 mM), with the most active compounds being , followed by and , affording IC of 0.55 ± 0.38 mM, 0.92 ± 0.10 mM, and 0.95 ± 0.14 mM, respectively. Preliminary structure-activity relationships revealed the importance of such substituents in enhancing the activity. Furthermore, the ADME screening test was applied to optimize the physicochemical properties and determine their drug-like characteristics. Binding interactions and stability between ligands and active residues of the investigated enzymes were confirmed through molecular docking and dynamic simulation study. These findings provided guidance for further developing leading new spiropyrrolidine scaffolds with improved dual antimicrobial and antidiabetic activities.
为了应对新兴的抗微生物耐药微生物，迫切需要开发具有更好治疗特性的新型抗菌药物。为此，设计、合成、表征了一系列 13 种新的螺吡咯烷衍生物，并评估了它们的体外抗菌、抗氧化和抗糖尿病潜力。抗菌结果表明，设计的化合物对临床分离株表现出良好的活性，其中 （MIC 3.95 mM 对 ATCC 25923）比四环素（MIC 576.01 mM）活性更强。抗氧化活性通过捕获 DPPH、ABTS 和 FRAP 测定法进行评估。结果表明，所有合成化合物都具有显著的抗氧化潜力，特别是 ，其 IC 为 3.26 ± 0.32 mM（DPPH）、7.03 ± 0.07 mM（ABTS）和 3.69 ± 0.72 mM（FRAP），表现出最强的活性。对它们的 -淀粉酶抑制作用进行测试，所检查的类似物显示出不同程度的 -淀粉酶活性，IC 范围在 0.55 ± 0.38 mM 和 2.19 ± 0.23 mM 之间，与阿卡波糖（IC 1.19 ± 0.02 mM）相比，最活跃的化合物是 ，其次是 和 ，IC 分别为 0.55 ± 0.38 mM、0.92 ± 0.10 mM 和 0.95 ± 0.14 mM。初步的构效关系表明，这些取代基在增强活性方面的重要性。此外，还应用了 ADME 筛选试验来优化物理化学性质并确定其类药性特征。通过分子对接和动态模拟研究证实了配体与研究酶的活性残基之间的结合相互作用和稳定性。这些发现为进一步开发具有改进的双重抗菌和抗糖尿病活性的新型螺吡咯烷骨架提供了指导。
