PDF(Pubmed)
Abstract：
The targeted compounds in this research, resveratrol analogs 1-14, were synthesized as mixtures of isomers by the Wittig reaction using heterocyclic triphenylphosphonium salts and various benzaldehydes. The planned compounds were those possessing the trans-configuration as the biologically active trans-resveratrol. The pure isomers were obtained by repeated column chromatography in various isolated yields depending on the heteroaromatic ring. It was found that butyrylcholinesterase (BChE) was more sensitive to the heteroaromatic resveratrol analogs than acetylcholinesterase (AChE), except for 6, the methylated thiophene derivative with chlorine, which showed equal inhibition toward both enzymes. Compounds 5 and 8 achieved the highest BChE inhibition with IC50 values of 22.9 and 24.8 μM, respectively. The same as with AChE and BChE, methylated thiophene subunits of resveratrol analogs showed better enzyme inhibition than unmethylated ones. Two antioxidant spectrophotometric methods, DPPH and CUPRAC, were applied to determine the antioxidant potential of new heteroaromatic resveratrol analogs. The molecular docking of these compounds was conducted to visualize the ligand-active site complexes\' structure and identify the non-covalent interactions responsible for the complex\'s stability, which influence the inhibitory potential. As ADME properties are crucial in developing drug product formulations, they have also been addressed in this work. The potential genotoxicity is evaluated by in silico studies for all compounds synthesized.
摘要：
本研究中的目标化合物，白藜芦醇类似物1-14通过使用杂环三苯基鳞盐和各种苯甲醛的Wittig反应合成为异构体的混合物。计划的化合物是具有反式构型作为生物活性反式白藜芦醇的化合物。通过重复的柱色谱法以取决于杂芳环的各种分离产率获得纯的异构体。发现丁酰胆碱酯酶（BChE）对杂芳族白藜芦醇类似物比乙酰胆碱酯酶（AChE）更敏感，除了6，与氯的甲基化噻吩衍生物，对两种酶的抑制作用相同。化合物5和8达到最高的BChE抑制，IC50值为22.9和24.8μM，分别。和AChE和BChE一样,白藜芦醇类似物的甲基化噻吩亚基比未甲基化的噻吩亚基表现出更好的酶抑制作用。两种抗氧化剂分光光度法，DPPH和CUPRAC,用于确定新的杂芳族白藜芦醇类似物的抗氧化潜力。进行这些化合物的分子对接，以可视化配体-活性位点复合物的结构，并确定负责复合物稳定性的非共价相互作用，影响抑制潜力。由于ADME特性在开发药物产品配方中至关重要，他们也在这项工作中得到了解决。通过对合成的所有化合物的计算机模拟研究来评估潜在的遗传毒性。
