Design, synthesis and evaluation of novel coumarin-oxa/thiadiazole hybrids as AChE inhibitors for the treatment of alzheimer's disease
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Title |
Design, synthesis and evaluation of novel coumarin-oxa/thiadiazole hybrids as AChE inhibitors for the treatment of alzheimer's disease
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Creator |
Jaber, Tasneem
More, Uttam A. Sidat, Parin Khan, Shabeena Jain, Payal N. Noolvi, Malleshappa B. Palkar, Mahesh |
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Subject |
Coumarin derivatives
Molecular docking Anti-Alzheimer Agents |
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Description |
483-493
The most prevalent type of dementia is Alzheimer's disease. It is a central nervous system neurodegenerative disease marked mostly by progressive cognitive dysfunction. One of the well-defined targets for Alzheimer's disease management is the acetylcholinesterase enzyme. Coumarins are phytochemicals found naturally in many plant species that have a variety of biological actions, including acetylcholinesterase inhibition. To accomplish this goal, several 7-hydroxy coumarin derivatives as acetylcholinesterase (AChE) inhibitors have been synthesized using Pechmann condensation and conjugation with various thiadiazole and oxadiazole. Spectral analysis has been used to characterize these molecules. An in silico docking investigation against the AChE enzyme PDB 4EY7 demonstrates that the molecule interacts with the CAS and PAS sites of the acetylcholinesterase enzyme. The coumarin moiety interacts with the PAS site, whereas the thiadiazole/oxadiazole moiety interacts with the CAS site. Knowing the pharmacophoric requirements for inhibiting AChE, compounds have been developed and evaluated for anti-Alzheimer efficacy in vitro utilizing the Ellman assay. With an IC50 of 0.75 μM, compound 9b have demonstrated great anti-Alzheimer efficacy. We conclude that the compounds described in this paper can be used to develop novel anti-Alzheimer agents. |
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Date |
2024-05-07T09:53:49Z
2024-05-07T09:53:49Z 2024-05 |
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Type |
Article
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Identifier |
0975-0991 (Online); 0971-457X (Print)
http://nopr.niscpr.res.in/handle/123456789/63865 https://doi.org/10.56042/ijct.v31i3.3786 |
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Language |
en
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Publisher |
NIScPR-CSIR, India
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Source |
IJCT Vol.31(3) [May 2024]
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