Mekky Ahmed E M, Sanad Sherif M H
Chemistry Department, Faculty of Science, Cairo University, 12613, Giza, Egypt.
Chem Biodivers. 2023 Apr;20(4):e202200518. doi: 10.1002/cbdv.202200518. Epub 2023 Mar 29.
Two series of piperazine-linked bis(chromene) hybrids that are attached to pyrazole units were synthesized in the current study. Both series are attached to an acyl unit at pyrazole-C3, with one series attached to an acetyl unit and the other to an ethoxycarbonyl unit. A [3+2] cycloaddition protocol was conducted to produce the target hybrids with good yields by reacting the appropriate hydrazonoyl chlorides with chromene-based bis(enaminone) in dioxane containing triethylamine at reflux for 4 h. New hybrids were tested for acetylcholinesterase inhibitory activity at concentrations of 15 and 25 μM, as well as their ability to quench 2,2-diphenylpicrylhydrazyl (DPPH) free radicals at a concentration of 25 μg/mL. In general, the inhibitory activity is related to the electronic properties of the para-substituent that is attached to the arene unit at pyrazole-N1. Furthermore, the acyl unit attached to pyrazole-C3 has a significant effect on the new hybrids' inhibitory activity. At the previous concentrations, the (3-acetylpyrazole)-linked hybrid attached to p-NO units demonstrated the best acetylcholinesterase inhibitory activity, with inhibition percentages of 79.7 and 90.2. Furthermore, the previous hybrid demonstrated the most effective DPPH inhibitory activity, with an inhibition percentage of 87.5.
在本研究中合成了与吡唑单元相连的两系列哌嗪连接的双（色烯）杂化物。这两个系列在吡唑-C3处均与一个酰基单元相连，其中一个系列与乙酰基单元相连，另一个与乙氧羰基单元相连。通过使适当的腙酰氯与基于色烯的双烯胺酮在含有三乙胺的二氧六环中回流反应4小时，采用[3+2]环加成方案以良好的产率制备目标杂化物。对新的杂化物进行了浓度为15和25μM时的乙酰胆碱酯酶抑制活性测试，以及浓度为25μg/mL时淬灭2,2-二苯基苦味酰基自由基（DPPH）的能力测试。一般来说，抑制活性与连接在吡唑-N1处芳烃单元上的对位取代基的电子性质有关。此外，连接在吡唑-C3上的酰基单元对新杂化物的抑制活性有显著影响。在上述浓度下，连接对硝基单元的（3-乙酰基吡唑）连接的杂化物表现出最佳的乙酰胆碱酯酶抑制活性，抑制率分别为79.7和90.2。此外，上述杂化物表现出最有效的DPPH抑制活性，抑制率为87.5。
