To elucidate the interaction mechanism of CNS selective carbamate-type cholinesterase (CHE) inhibitor rivastigmine with dsDNA by multi-spectroscopic, electrochemical, and viscosimetric methods

Abstract

Alzheimer's disease (AD) is one of the major causes of death, affecting the elderly most and a type of dementia. Cell death in the brain caused by neurodegenerative disorders is suggested as the leading cause of AD. Over time, it impairs the patient's cognitive function, learning capacity, and ability to remember new information, leading to speech impairment and death. Inadequate symptomatic therapies may intensify these challenges, and without Alzheimer's therapy, the number of people dying from dementia over the age of 75 roughly doubles every 20 years. Although there is no treatment for Alzheimer's disease, acetylcholinesterase inhibitors like Rivastigmine tartrate, Galantamine, and Donepezil can help lessen the effects of cholinesterases and temporarily relieve symptoms. In recent years, scientists have been working to develop and advance potential treatments and clinical trials for Alzheimer's disease. Rivastigmine tartrate (RT) is a carbamate derivative and a cholinesterase inhibitor with a chemical formula of C18H28N2O8. It is used for the treatment of mild to moderate Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). As a cholinesterase inhibitor, RT inhibits both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes, increasing the reversible inhibition of acetylcholine breakdown by cholinesterase and so raising the amount of ACh in the brain and promoting cholinergic function. Leading to this mechanism of action, RT in both oral and transdermal path forms is used to relieve the symptoms of Alzheimer's patients. Characterizing and interpreting the processes, binding modalities to DNA or RNA, and potential toxicity locations of these medicines are thought to be important subjects for pharmaceutical and biochemical studies. In the literature research, we have done, no interaction mechanism between RT and double-stranded deoxyribonucleic acid (dsDNA) has been encountered so far. For this reason, the interaction mechanism between RT and dsDNA has been examined using different analytical techniques, considering the possibility that it may contribute to the healthier and higher life quality of users, with the thought that possible side effects can be evaluated. This study used a variety of analytical and multi-spectroscopic methods under physiological conditions to investigate the mechanism of interaction between RT and dsDNA, including UV, fluorescence, thermal denaturation, electrochemical, and viscosity measurements. Based on all described techniques, the results showed that RT binds to dsDNA via the minor groove binding mode.