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-NO2 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.
Keywords: DPPH antioxidant activity; [3+2] cycloaddition reactions; acetylcholinesterase inhibitors; piperazine-chromene hybrids; pyrazoles.
© 2023 Wiley-VHCA AG, Zurich, Switzerland.