新型二氢查尔酮衍生苄胺的胆碱酯酶抑制活性、碳酸酐酶抑制活性及计算机模拟研究。
Cholinesterases, carbonic anhydrase inhibitory properties and in silico studies of novel substituted benzylamines derived from dihydrochalcones.
机构信息
Agri Ibrahim Cecen University, Central Researching Laboratory, 04100 Agri, Turkey.
Atatürk University, Faculty of Science, Department of Chemistry, Erzurum, Turkey.
出版信息
Comput Biol Chem. 2021 Oct;94:107565. doi: 10.1016/j.compbiolchem.2021.107565. Epub 2021 Aug 20.
A series of novel urea, sulfamide and N,N-dipropargyl substituted benzylamines were synthesized from dihydrochalcones. The synthesized compounds were evaluated for their cholinesterases and carbonic anhydrase inhibitory actions. The known dihydrochalcones were converted into four new benzylamines via reductive amination. N,N-Dipropargylamines, ureas and sulfamides were synthesized following the reactions of benzylamines with propargyl bromide, N,N-dimethyl sulfamoyl chloride and N,N-dimethyl carbamoyl chloride. The novel substituted benzylamines derived from dihydrochalcones were evaluated against some enzymes such as human erythrocyte carbonic anhydrase I and II isoenzymes (hCA I and hCA II), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The novel substituted benzylamines derived from dihydrochalcones exhibited K values in the range of 0.121-1.007 nM on hCA I, and 0.077-0.487 nM on hCA II closely related to several pathological processes. On the other hand, K values were found in the range of 0.112-0.558 nM on AChE, 0.061-0.388 nM on BChE. As a result, novel substituted benzylamines derived from dihydrochalcones showed potent inhibitory profiles against indicated metabolic enzymes. In addition, Induced-Fit Docking (IFD) simulations and ADME prediction studies have also been carried out to elucidate the inhibition mechanisms and drug-likeness of the synthesized compounds. Therefore, these results can make significant contributions to the treatment of some global diseases, especially Alzheimer's diseases and glaucoma, and the development of new drugs.
一系列新型的脲、磺酰胺和 N,N-二炔丙基取代的苄胺是由二氢查耳酮合成的。合成的化合物被评估为其胆碱酯酶和碳酸酐酶抑制作用。已知的二氢查耳酮通过还原胺化转化为四种新的苄胺。N,N-二炔丙基胺、脲和磺酰胺是通过苄胺与炔丙基溴、N,N-二甲基磺酰胺氯和 N,N-二甲基氨基甲酰氯反应合成的。从二氢查耳酮衍生的新型取代苄胺被评估了对一些酶的抑制作用，如人红细胞碳酸酐酶 I 和 II 同工酶（hCA I 和 hCA II）、乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）。从二氢查耳酮衍生的新型取代苄胺对 hCA I 的 K 值范围为 0.121-1.007 nM，对 hCA II 的 K 值范围为 0.077-0.487 nM，与几种病理过程密切相关。另一方面，在 AChE 上的 K 值范围为 0.112-0.558 nM，在 BChE 上的 K 值范围为 0.061-0.388 nM。因此，从二氢查耳酮衍生的新型取代苄胺对指示代谢酶表现出有效的抑制作用。此外，还进行了诱导契合对接（IFD）模拟和 ADME 预测研究，以阐明合成化合物的抑制机制和药物相似性。因此，这些结果可以为治疗一些全球性疾病，特别是阿尔茨海默病和青光眼，以及开发新药做出重要贡献。
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