Department of Chemistry, Faculty of Arts and Sciences, Muş Alparslan University, 49250, Muş, Turkey.
Department of Food Processing, Technical Science Vocational School, Muş Alparslan University, 49250, Muş, Turkey.
Mol Divers. 2022 Oct;26(5):2459-2472. doi: 10.1007/s11030-021-10344-x. Epub 2021 Nov 7.
Schiff bases are well-known compounds for having significant biological properties. In this study, a new Schiff base ligand and its metal complexes were synthesized, and their antioxidant and enzyme inhibitory activities were evaluated. The new Schiff base ligand was synthesized with the condensation reaction of 6-tert-butyl 3-ethyl 2-amino-4,5-dihydrothieno[2,3-c]pyridine-3,6(7H)-dicarboxylate and 2-hydroxybenzaldehyde compounds. Fe(II), Co(II), and Ni(II) metal complexes of the novel Schiff base ligand were synthesized and characterized. The purity and molecular formula of the synthesized compounds were identified with elemental analysis, infrared, ultraviolet-visible, mass spectrophotometry, powder XRD, magnetic and thermal measurements. The Schiff base acted as a three dentate chelate. The analytical and spectroscopic data suggested an octahedral geometry for the complexes. The in vitro antioxidant method studies elucidated a more effective antioxidant character of the Schiff base ligand than its metal complexes but a less effective antioxidant potential than the standard antioxidant compounds. The enzyme inhibition potentials of the synthesized compounds for AChE, BChE, and GST enzymes were determined by in vitro enzyme activity methods. The Schiff base ligand was discovered to be the best inhibitor for the AChE and BChE with the values of 7.13 ± 0.84 µM and 5.75 ± 1.03 µM K, respectively. Moreover, the Fe(II) complex displayed the best K value as 9.37 ± 1.06 µM for the GST enzyme. Finally, molecular docking studies were carried out to see the structural interactions of the compounds. The metal complexes demonstrated better binding affinities with the AChE, BChE, and GST enzymes than the Schiff base ligand. This study identified a potential Schiff base molecule against both AChE and BChE targets to further investigate for in vivo and safety evaluation.
席夫碱是一类具有重要生物活性的化合物。本研究合成了一种新的席夫碱配体及其金属配合物，并对其抗氧化和酶抑制活性进行了评价。新的席夫碱配体是通过 6-叔丁基 3-乙基 2-氨基-4,5-二氢噻吩并[2,3-c]吡啶-3,6(7H)-二羧酸酯与 2-羟基苯甲醛化合物的缩合反应合成的。合成了新型席夫碱配体的 Fe(II)、Co(II)和 Ni(II)金属配合物，并对其进行了表征。通过元素分析、红外、紫外可见、质谱、粉末 XRD、磁性和热测量确定了合成化合物的纯度和分子式。席夫碱作为三齿螯合剂。分析和光谱数据表明，配合物具有八面体几何构型。体外抗氧化方法研究表明，席夫碱配体的抗氧化活性强于其金属配合物，但抗氧化潜力弱于标准抗氧化化合物。通过体外酶活性方法测定了合成化合物对 AChE、BChE 和 GST 酶的酶抑制潜力。结果表明，席夫碱配体对 AChE 和 BChE 的抑制作用最强，其 K 值分别为 7.13±0.84 μM 和 5.75±1.03 μM。此外，Fe(II)配合物对 GST 酶的 K 值为 9.37±1.06 μM。最后，进行了分子对接研究，以观察化合物的结构相互作用。金属配合物与 AChE、BChE 和 GST 酶的结合亲和力均优于席夫碱配体。本研究鉴定了一种潜在的席夫碱分子，可作为 AChE 和 BChE 的双重靶点，进一步进行体内和安全性评价。
