Department of Chemistry, University of Malaya, Kuala Lumpur, Malaysia.
Molecules. 2011 Nov 7;16(11):9316-30. doi: 10.3390/molecules16119316.
Some novel Schiff bases derived from 1-(2-ketoiminoethyl)piperazines were synthesized and characterized by mass spectroscopy, FTIR, UV-Visible, 1H and 13C-NMR. The compounds were tested for inhibitory activities on human acetylcholinesterase (hAChE), antioxidant activities, acute oral toxicity and further studied by molecular modeling techniques. The study identified the compound (DHP) to have the highest activity among the series in hAChE inhibition and DPPH assay while the compound LP revealed the highest activity in the FRAP assay. The hAChE inhibitory activity of DHP is comparable with that of propidium, a known AChE inhibitor. This high activity of DHP was checked by molecular modeling which showed that DHP could not be considered as a bivalent ligand due to its incapability to occupy the esteratic site (ES) region of the 3D crystal structure of hAChE. The antioxidant study unveiled varying results in 1,1-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. This indicates mechanistic variations of the compounds in the two assays. The potential therapeutic applications and safety of these compounds were suggested for use as human acetylcholinesterase inhibitors and antioxidants.
一些新的席夫碱来源于 1-(2-酮亚氨基乙基)哌嗪，并通过质谱、FTIR、UV-可见、1H 和 13C-NMR 进行了表征。这些化合物被测试了对人乙酰胆碱酯酶（hAChE）的抑制活性、抗氧化活性、急性口服毒性，并进一步通过分子建模技术进行了研究。研究发现，在 hAChE 抑制和 DPPH 测定中，该系列化合物中（DHP）的活性最高，而 LP 化合物在 FRAP 测定中显示出最高的活性。DHP 对 hAChE 的抑制活性可与已知的 AChE 抑制剂丙啶相媲美。这种高活性通过分子建模得到了验证，结果表明 DHP 不能被认为是双价配体，因为它不能占据 hAChE 的立体化学位点（ES）区域。抗氧化研究在 1,1-二苯基-1-苦基肼（DPPH）和铁还原抗氧化能力（FRAP）测定中显示出不同的结果。这表明化合物在两种测定中的作用机制不同。这些化合物具有作为人乙酰胆碱酯酶抑制剂和抗氧化剂的潜在治疗应用和安全性。
