Investigation of inhibition effects on acetylcholinesterase, butyrylcholinesterase enzymes and antibacterial activities of piperidine derived compounds

Alzheimer's is a very common dementia disease recently and there is no cure. Acetylcholine is the neurotransmitter that decreases most in this disease, which causes a decrease in neurotransmitters in the brain. The degradation of acetylcholine must be reduced in order to treat or prevent the disease, but this is only possible with the inhibition of astilcholinesterase (AChE), which degrades acetylcholine. Although the pharmacological role of butyrylcholinesterase (BChE) has not been determined with scientific research yet, it has been reported that the enzyme may have a balancing role during degenerative changes and acetylcholine hydrolysis in the brain. Cholinesterase inhibitors such as Tacrine and Rivastigmine are currently used for treatment and they have many known side effects. Donepezil, which is in the structure of piperidine and used as a drug in the treatment of Alzheimer's, is more selective than other drugs, with less side effects. its high specificity fo acetylcholinesterases in the central nervous system is an important advantage of the drug. Many piperidine derivatives such as donepezil constitute the basic structure of pharmacologically active compounds and important drugs. In our study, the inhibition effects of piperidine derivative (1-methyl-4-hydroxy-4- phenylpiperidin-3yl)methanone, (1-ethyl-4-hydroxy-4-phenylpiperidin-3yl)methanone compounds on AChE and BChE enzymes were examined in vitro, IC50 and ki values were calculated and inhibition types were determined. At the same time, the antibacterial activity of the compounds on 7 different strains was determined. Ampicillin / Sulbactam and bacitracin were used as positive controls. IC50 values (AChE: 4.584 M; BChE: 51.448M) and ki values (AChE: 0.00344±0.00071; BChE: 0.05406±0.01009) for (1-methyl-4-hydroxy-4-phenylpiperidin- 3yl)methanone compound; IC50 values (AChE: 4.312 M; BChE: 47.968 M) and ki values (AChE: 0.003047±0.00060; BChE: 0.04404±0.05109) for (1-ethyl-4-hydroxy-4- phenylpiperidin-3yl)methanone compound were calculated. The inhibition types of the substances were determined as noncompetitive. It was determined that the inhibition effects on the AChE enzyme were much higher in the two compounds of piperidine derivatives, and they inhibited the BChE enzyme at a lower level. Since BChE acts as a correlator in cholinergic transmission in the deficiency and absence of AChE, it is thought that such dual inhibitors may provide longer-term efficacy than AChE selective agents and are therefore important for Alzheimer's disease. At the same time, it is thought that all the results obtained may be a guide for the determination of active substances in the field of pharmacology and for new studies to be carried out, since these compounds form a higher zone diameter than antibiotics on most of the strains studied and have strong antibacterial activity.