| dc.contributor.author | Kumar, B | |
| dc.contributor.author | Dwivedi, A.R | |
| dc.contributor.author | Sarkar, B | |
| dc.contributor.author | Gupta, S.K | |
| dc.contributor.author | Krishnamurthy, S | |
| dc.contributor.author | Mantha, Anil K | |
| dc.contributor.author | Parkash, Jyoti | |
| dc.contributor.author | Kumar, Vinod | |
| dc.date.accessioned | 2019-09-03T09:41:19Z | |
| dc.date.available | 2019-09-03T09:41:19Z | |
| dc.date.issued | 2019 | |
| dc.identifier.citation | Kumar, B., Dwivedi, A.R.and Sarkar, B. et.al.4,6-Diphenylpyrimidine Derivatives as Dual Inhibitors of Monoamine Oxidase and Acetylcholinesterase for the Treatment of Alzheimer's Disease.10(1).PP.252-265.10.1021/acschemneuro.8b00220 | en_US |
| dc.identifier.issn | 19487193 | |
| dc.identifier.uri | http://kr.cup.edu.in/handle/32116/2450 | |
| dc.description.abstract | Alzheimer's disease (AD) is a neurodegenerative disorder with multifactorial pathogenesis. Monoamine oxidase (MAO) and acetylcholinesterase enzymes (AChE) are potential targets for the treatment of AD. A total of 15 new propargyl containing 4,6-diphenylpyrimidine derivatives were synthesized and screened for the MAO and AChE inhibition activities along with ROS production inhibition and metal-chelation potential. All the synthesized compounds were found to be selective and potent inhibitors of MAO-A and AChE enzymes at nanomolar concentrations. VB1 was found to be the most potent MAO-A and BuChE inhibitor with IC 50 values of 18.34 ± 0.38 nM and 0.666 ± 0.03 μM, respectively. It also showed potent AChE inhibition with an IC 50 value of 30.46 ± 0.23 nM. Compound VB8 was found to be the most potent AChE inhibitor with an IC 50 value of 9.54 ± 0.07 nM and displayed an IC 50 value of 1010 ± 70.42 nM against the MAO-A isoform. In the cytotoxic studies, these compounds were found to be nontoxic to the human neuroblastoma SH-SY5Y cells even at 25 μM concentration. All the compounds were found to be reversible inhibitors of MAO-A and AChE enzymes. In addition, these compounds also showed good neuroprotective properties against 6-OHDA- and H 2 O 2 -induced neurotoxicity in SH-SY5Y cells. All the compounds accommodate nicely to the hydrophobic cavity of MAO-A and AChE enzymes. In the molecular dynamics simulation studies, both VB1 and VB8 were found to be stable in the respective cavities for 30 ns. Thus, 4,6-diphenylpyrimidine derivatives can act as promising leads in the development of dual-acting inhibitors targeting MAO-A and AChE enzymes for the treatment of Alzheimer's disease. © 2018 American Chemical Society. | en_US |
| dc.language.iso | en | en_US |
| dc.publisher | American Chemical Society | en_US |
| dc.subject | acetylcholinesterase inhibitors | en_US |
| dc.subject | Alzheimer's disease | en_US |
| dc.subject | diphenylpyrimidine | en_US |
| dc.subject | dual inhibitors | en_US |
| dc.subject | MAO inhibitors | en_US |
| dc.subject | neuroprotective agents | en_US |
| dc.title | 4,6-Diphenylpyrimidine Derivatives as Dual Inhibitors of Monoamine Oxidase and Acetylcholinesterase for the Treatment of Alzheimer's Disease | en_US |
| dc.type | Article | en_US |
| dc.identifier.doi | 10.1021/acschemneuro.8b00220 | |
| dc.identifier.url | https://pubs.acs.org/doi/abs/10.1021/acschemneuro.8b00220 | |
| dc.title.journal | ACS Chemical Neuroscience | en_US |
| dc.type.accesstype | Closed Access | en_US |
