Chemistry Department, Faculty of Arts and Science, Dumlupınar University, 43100 Kütahya, Turkey.
Department of Pharmaceutical and Analytical Chemistry, Faculty of Pharmacy, Bezmialem Vakif University, 34093 Istanbul, Turkey.
Bioorg Chem. 2017 Feb;70:245-255. doi: 10.1016/j.bioorg.2017.01.005. Epub 2017 Jan 9.
A novel series of tacrine derivatives containing sulfonamide group were synthesized and their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were evaluated. The result showed that all the synthesized tacrine-sulfonamides (VIIIa-o) exhibited inhibitory activity on both cholinesterases. VIIIg showed the highest inhibitory activity on AChE IC=0.009μM. This value is 220-fold greater than that of galantamine (IC=2.054μM) and 6-fold greater than tacrine (IC=0.055μM). VIIIf displayed the strongest inhibition of BuChE (IC=2.250μM), which is close to donepezil (IC=2.680μM) and 8-fold greater than that of galantamine (IC=18.130μM) Furthermore, all of the synthesized tacrine derivatives showed higher inhibition of BuChE than that of galantamine. In addition, the cupric reducing antioxidant capacities (CUPRAC) and ABTS cation radical scavenging abilities of the synthesized compounds were investigated for the antioxidant activity. Among them, VIIIb (IC=94.390±2.310μM) showed significantly better ABTS cation radical scavenging ability than all of the new synthesized compounds.
一系列新型含磺酰胺基的他克林衍生物被合成出来，并评估了它们对乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）的抑制作用。结果表明，所有合成的他克林-磺酰胺类化合物（VIIIa-o）均对两种胆碱酯酶均具有抑制活性。VIIIg 对 AChE 的抑制活性最高（IC=0.009μM）。这一数值比加兰他敏（IC=2.054μM）高 220 倍，比他克林（IC=0.055μM）高 6 倍。VIIIf 对 BuChE 的抑制作用最强（IC=2.250μM），与多奈哌齐（IC=2.680μM）接近，比加兰他敏（IC=18.130μM）高 8 倍。此外，所有合成的他克林衍生物对 BuChE 的抑制作用均高于加兰他敏。此外，还研究了合成化合物的铜还原抗氧化能力（CUPRAC）和 ABTS 阳离子自由基清除能力，以评估其抗氧化活性。其中，VIIIb（IC=94.390±2.310μM）对 ABTS 阳离子自由基的清除能力明显优于所有新合成的化合物。
