Piperazine derivatives with potent drug moiety as efficient acetylcholinesterase, butyrylcholinesterase, and glutathione S‐transferase inhibitors

Abstract Cholinesterases catalyze the breakdown of the neurotransmitter acetylcholine (ACh), a naturally occurring neurotransmitter, into choline and acetic acid, allowing the nervous system to function properly. In the human body, cholinesterases come in two types, including acetylcholinesterase (AChE; E.C.3.1.1.7) and butyrylcholinesterase (BChE; E.C.3.1.1.8). Both cholinergic enzyme inhibitors are essential in the biochemical processes of the human body, notably in the brain. On the other hand, GSTs are found all across nature and are the principal Phase II detoxifying enzymes in eukaryotes and prokaryotes. Specific isozymes are identified as therapeutic targets because they are overexpressed in various malignancies and may have a role in the genesis of other diseases such as neurological disorders, multiple sclerosis, asthma, and especially cancer cell. Piperazine chemicals have a role in many biological processes and have fascinating pharmacological properties. As a result, therapeutically effective piperazine research is becoming more prominent. Half maximal inhibition concentrations (IC 50 ) of piperazine derivatives were found in ranging of 4.59–6.48 µM for AChE, 4.85–8.35 µM for BChE, and 3.94‐8.66 µM for GST. Also, piperazine derivatives exhibited Ki values of 8.04 ± 5.73–61.94 ± 54.56, 0.24 ± 0.03–32.14 ± 16.20, and 7.73 ± 1.13–22.97 ± 9.10 µM toward AChE, BChE, and GST, respectively. Consequently, the inhibitory properties of the AChE/BChE and GST enzymes have been compared to Tacrine (for AChE and BChE) and Etacrynic acid (for GST).