Recent Advances in the Chemistry of Current Drugs and Prospective Molecules for Treatment of Alzheimer’s Disease

Posted: 7 Feb 2020 Last revised: 16 Feb 2020

See all articles by Rajlaxmi Deshpande

Rajlaxmi Deshpande

SPPSPTM, SVKM'S NMIMS

Somil Shah

SPPSPTM, SVKM'S NMIMS

Harish Kundaikar

SPPSPTM, SVKM'S NMIMS

Date Written: January 24, 2020

Abstract

Alzheimer’s Disease (AD) is an irreversible, chronic degenerative disease that slowly destroys memory and thinking skills, and eventually destroys the ability to carry out the simplest of day-to-day routine tasks. This disease is characterised by loss of neurons and synapses in the cerebral cortex and certain subcortical regions. Presence of beta-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) in brains of the affected patients are the distinguishable characteristics of this disease. Currently, no treatment is available to stop or reverse progression of AD, though it may temporarily improve symptoms. There are four USFDA approved drugs which are helpful for symptomatic treatment in AD namely Donepezil, Rivastigmine, Galantamine and Memantine. Memantine functions as an NMDA receptor antagonist, whereas the other three drugs act by inhibiting the acetylcholinesterase enzyme (AChE) resulting in an increase in the levels of acetylcholine (ACh) in the body.

In the past decades, many advancements in the current drugs as well as the experimental drugs for AD have been made and these involve structural modifications and mechanistic improvements to increase the capacity of the molecules to cross the blood brain barrier (BBB). Synthesis of 2-acetylphenol-donepezil hybrids is an example of an approach which was adopted based on Multi-Target Directed Ligand (MTDL) strategy. Recently, synthesis of salicylanilide N-alkyl carbamates was carried out and these were observed to possess higher AChE inhibiting capacity than Rivastigmine. Memogain is an inactive prodrug of galantamine which has shown improved effectiveness, fewer side effects and due to its lipophilic nature is said to penetrate the BBB where it gets cleaved into active galantamine. Huperzine A is another highly selective AChE inhibitor and is approved for use only in China though not by USFDA. Tacrine and Huperazine A were combined together to form a hybrid molecule Huprine X, which is said to possess not only potency but also higher selectivity for AChE inhibition alongside anti-Aβ properties.

In this poster, we will discuss the ongoing research on the structural advancements of the approved drugs and related compounds towards obtaining newer and better drugs for AD therapy.

Keywords: Alzheimer's disease, therapeutics, Donepezil, Rivastigmine, Galantamine, Memantine, Tacrine, Huperzine A, Aβ, NFT, Acetylcholinesterases, NMDA

Suggested Citation

Deshpande, Rajlaxmi and Shah, Somil and Kundaikar, Harish, Recent Advances in the Chemistry of Current Drugs and Prospective Molecules for Treatment of Alzheimer’s Disease (January 24, 2020). Proceedings of International Conference on Drug Discovery (ICDD) 2020, Available at SSRN: https://ssrn.com/abstract=3533041

Rajlaxmi Deshpande

SPPSPTM, SVKM'S NMIMS ( email )

V. L. Mehta Road
Vile Parle
Mumbai, Maharashtra 400056
India
02242332010 (Phone)

Somil Shah

SPPSPTM, SVKM'S NMIMS ( email )

V.L.Mehta Road
Vile Parle (W)
Mumbai, Maharashtra 400056
India
02242332010 (Phone)

Harish Kundaikar (Contact Author)

SPPSPTM, SVKM'S NMIMS ( email )

V. L. Mehta Road
Vile Parle
Mumbai, Maharashtra 400056
India
02242332010 (Phone)

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