Pentafluorobenzyl-substituted benzimidazolium salts: Synthesis, characterization, crystal structures, computational studies and inhibitory properties of some metabolic enzymes
Pentafluorobenzyl-substituted benzimidazolium salts: Synthesis, characterization, crystal structures, computational studies and inhibitory properties of some metabolic enzymes
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DOI：
10.1016/j.molstruc.2022.133266
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发表时间：
2022-06-02
影响因子：
3.8
通讯作者：
Gulcin, Ilhami
中科院分区：
文献类型：
--
作者：
Hamide, Mahmut;Gok, Yetkin;Gulcin, Ilhami
这项工作包括五氟苄基取代的苯并咪唑鎓盐（其为N -杂环卡宾（NHC）前体）的合成与表征。所有化合物均通过1H、13C和19F核磁共振、傅里叶变换红外光谱以及元素分析技术进行了表征。所有的光谱和元素分析数据完全证实了所提出的分子式。在合成的化合物中，1 -（2 -甲基苄基）- 3 -（2,3,4,5,6 -五氟苄基）苯并咪唑鎓溴化物（1b）、1 -（4 -甲基苄基）- 3 -（2,3,4,5,6 -五氟苄基）苯并咪唑鎓溴化物（1d）和1 -（4 -三氟甲基苄基）- 3 -（2,3,4,5,6 -五氟苄基）苯并咪唑鎓溴化物（1f）的分子结构通过单晶X射线衍射研究得以阐明。经过酶抑制研究，一系列新的五氟苄基取代的NHC前体被确定为乙酰胆碱酯酶（AChE）和碳酸酐酶（hCAs）同工酶的高效抑制剂。对于AChE，Ki值在7.20 ± 1.31到28.26 ± 5.72 nM范围内；对于作为原核生物和真核生物中普遍存在的含金属酶的hCA I，Ki值在10.25 ± 0.93到40.93 ± 3.89 nM之间；对于作为治疗阿尔茨海默病等神经系统疾病的关键酶的hCA II，Ki值在3.33 ± 0.15到58.22 ± 6.99 nM之间。对化合物进行的分子对接研究表明，基于针对AChE和hCAs的结合能和相互作用类型，一系列新的五氟苄基取代的NHC前体具有更高的潜在抑制特性。（c）2022爱思唯尔有限公司。保留所有权利。
This work contains the synthesis and characterization of the pentafluorobenzyl-substituted benzimidazolium salts which N -heterocyclic carbene (NHC) precursors. All compounds were characterized by using 1 H, 13 C, and 19 F NMR, FT-IR spectroscopy, and elemental analysis techniques. All the spectroscopy and elemental analysis data fully confirm the proposed formulas. In the synthesized compounds, the molecular structures of compounds 1-(2-methylbenzyl)-3-(2,3,4,5,6-pentafluorobenzyl)benzimidazolium bromide ( 1b ), 1-(4-methylbenzyl)-3-(2,3,4,5,6-pentafluorobenzyl)benzimidazolium bromide ( 1d ) and 1-(4-trifluoromethylbenzyl)-3-(2,3,4,5,6-pentafluorobenzyl)benzimidazolium bromide ( 1f ) were enlightened by single crystal X-ray diffraction studies. After enzyme inhibition study, a new series of pentafluorobenzyl-substituted NHC precursors were determined to be highly potent inhibitors for acetylcholinesterase (AChE) enzyme and carbonic anhydrases (hCAs) isoenzymes. K i values were found in the range of 7.20 +/- 1.31 to 28.26 +/- 5.72 nM for AChE , 10.25 +/- 0.93 to 40.93 +/- 3.89 nM toward hCA I as pervasive metal containing enzymes present in prokaryotes and eukaryotes, and 3.33 +/- 0.15 to 58.22 +/- 6.99 nM for hCA II as the key enzyme promising strategy for the treatment of neurological disorders such as Alzheimer's disease. The molecular docking study performed for compounds had higher potential inhibitory properties involved in a novel series of pentafluorobenzyl-substituted NHC precursors based on the binding energy and interaction types against AChE and hCAs. (c) 2022 Elsevier B.V. All rights reserved.