新型 N-取代硫代脒的绿色合成及分子对接：作为碳酸酐酶和乙酰胆碱酯酶有效抑制剂。
The green synthesis and molecular docking of novel N-substituted rhodanines as effective inhibitors for carbonic anhydrase and acetylcholinesterase enzymes.
机构信息
Department of Chemistry, Faculty of Sciences and Arts, Bingol University, 12000-Bingöl, Turkey.
Department of Biochemistry, Faculty of Veterinary Medicine, Bingol University, 12000-Bingöl, Turkey.
出版信息
Bioorg Chem. 2019 Sep;90:103096. doi: 10.1016/j.bioorg.2019.103096. Epub 2019 Jul 2.
Recently, inhibition effects of enzymes such as acetylcholinesterase (AChE) and carbonic anhydrase (CA) has appeared as a promising approach for pharmacological intervention in a variety of disorders such as epilepsy, Alzheimer's disease and obesity. For this purpose, novel N-substituted rhodanine derivatives (RhAs) were synthesized by a green synthetic approach over one-pot reaction. Following synthesis the novel compounds, RhAs derivatives were tested against AChE and cytosolic carbonic anhydrase I, and II (hCAs I, and II) isoforms. As a result of this study, inhibition constant (Ki) were found in the range of 66.35 ± 8.35 to 141.92 ± 12.63 nM for AChE, 43.55 ± 14.20 to 89.44 ± 24.77 nM for hCA I, and 16.97 ± 1.42 to 64.57 ± 13.27 nM for hCA II, respectively. Binding energies were calculated with docking studies as -5.969, -5.981, and -9.121 kcal/mol for hCA I, hCA II, and AChE, respectively.
最近，乙酰胆碱酯酶（AChE）和碳酸酐酶（CA）等酶的抑制作用作为治疗多种疾病（如癫痫、阿尔茨海默病和肥胖症）的药理学干预方法已经出现。为此，我们采用一锅法绿色合成方法合成了新型 N-取代的罗丹宁衍生物（RhAs）。合成新型化合物后，我们对 RhAs 衍生物进行了乙酰胆碱酯酶和胞质碳酸酐酶 I、II（hCAs I、II）同工酶的抑制活性测试。研究结果表明，对 AChE 的抑制常数（Ki）范围为 66.35±8.35 至 141.92±12.63 nM，对 hCA I 的抑制常数（Ki）范围为 43.55±14.20 至 89.44±24.77 nM，对 hCA II 的抑制常数（Ki）范围为 16.97±1.42 至 64.57±13.27 nM。通过对接研究计算了结合能，分别为 hCA I、hCA II 和 AChE 的-5.969、-5.981 和-9.121 kcal/mol。
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