Design of potent inhibitors of acetylcholinesterase using morin as the starting compound

One of the biggest challenges facing the research community in searching for a cure to Alzheimer's Disease (AD) is that there is not just one cause behind the disease; there are a complex combination of processes occurring in the brain leading to the breakdown of cognitive function and memory loss characteristic of Alzheimer's. For example, AD can be traced to extracellular amyloid plaques containing amyloid beta (Aβ) peptide and intracellular neurofibrillary tangles of hyperphosphorylated tau proteins in the brain of afflicted patients. Additionally, the role of acetylcholinesterase (AChE) in producing the rapid hydrolysis of acetylcholine (ACh)—the compound responsibly for maintaining neural transmissions—has been given much attention. Free radical damage and oxidative stress have also been identified as key causes in the onset of the symptoms typically associated with AD. Because there are multiple causes, each having its own biological mechanism, finding a cure proves challenging since any therapy must address all of these processes. To date, most of the drugs developed have targeted AChE inhibition with the understanding that increased ACh can repair cognitive function. However, while this approach helps to relieve some of the symptoms of AD, it does not ultimately cure the disease, leaving room for needed additional studies into the matter.

Flavonoids have been given particular attention in the search for a cure to AD because of their known role in reducing inflammation and oxidative stress. Some flavonols have been identified as effective inhibitors of AChE activity. Because of the unique properties of these compounds, they present an interesting opportunity to researchers looking for an effective treatment for AD as they attend to some of the key processes that bring on AD and its symptoms. In their study, Remya et al. decided to look at the role of morin -a flavonol- to see if it is effective in inhibiting AChE activity, as well as mitigating oxidative stress. To perform these tests, they used the Amplite Colorimetric Acetylcholinesterase Assay Kit which uses DTNB to accurately quantify the thiolcholine produced from the hydrolysis of acetylthiolcholine by AChE. Reyma and his team also modified morin in a variety of different ways to try and find the most effective treatment.

The results indicated that morin is an effective AChE inhibitor, but also found that some of the derivatives resulting from in silico structural modifications were even more effective. This is significant as it offers a new option for a base compound in the development of an anti-AD therapy. Studies like these are a huge step forward in the search for a cure, and they are made possible by the clear and reliable results obtained from materials such as the Amplite Colorimetric Acetylcholinesterase Assay Kit. When using materials like this, confidence levels can be high, allowing the research community to firmly move forward, closer and closer to a cure.

References

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1. Remya, C., et al. "Design of potent inhibitors of acetylcholinesterase using morin as the starting compound." Frontiers in Life Science 6.3-4 (2012): 107-117.