Publication Type : Journal Article
Publisher : Environmental Science and Pollution Research
Source : Environmental Science and Pollution Research, 2021, 28(29), pp. 38855-38866
Url : https://link.springer.com/article/10.1007/s11356-021-13320-y
Campus : Kochi
School : School of Pharmacy
Department : Pharmaceutical Chemistry & Analysis
Year : 2021
Abstract : Eleven piperazine-containing 1,3-diphenylprop-2-en-1-one derivatives (PC1-PC11) were evaluated for their inhibitory activities against monoamine oxidases (MAOs), cholinesterases (ChEs), and β-site amyloid precursor protein cleaving enzyme 1 (BACE-1) with a view toward developing new treatments for neurological disorders. Compounds PC10 and PC11 remarkably inhibited MAO-B with IC50 values of 0.65 and 0.71 μM, respectively. Ten of the eleven compounds weakly inhibited AChE and BChE with > 50% of residual activities at 10 μM, although PC4 inhibited AChE by 56.6% (IC50 = 8.77 μM). Compound PC3 effectively inhibited BACE-1 (IC50 = 6.72 μM), and PC10 and PC11 moderately inhibited BACE-1 (IC50 =14.9 and 15.3 μM, respectively). Reversibility and kinetic studies showed that PC10 and PC11 were reversible and competitive inhibitors of MAO-B with Ki values of 0.63 ± 0.13 and 0.53 ± 0.068 μM, respectively. ADME predictions for lead compounds revealed that PC10 and PC11 have central nervous system (CNS) drug-likeness. Molecular docking simulations showed that fluorine atom and trifluoromethyl group on PC10 and PC11, respectively, interacted with the substrate cavity of the MAO-B active site. Our results suggested that PC10 and PC11 can be considered potential candidates for the treatment of neurological disorders such as Alzheimer’s disease and Parkinson’s disease.
Cite this Research Publication : Bijo Mathew, Oh, J. Min, Baty, R. S., Batiha, G. El- Saber, Parambi, D. Grace Thom, Gambacorta, N., Nicolotti, O., and Kim, H., “Piperazine-substituted chalcones: a new class of MAO-B, AChE, and BACE-1 inhibitors for the treatment of neurological disorders”, Environmental Science and Pollution Research, 2021, 28(29), pp. 38855-38866.