A REVIEW ON INDOLE–CHALCONE DERIVATIVES AS POTENTIAL MULTITARGET THERAPEUTIC AGENTS FOR ALZHEIMER’S DISEASE

Author

Ms. Devika K, Mr. Arun Ramachandran


Abstract

 Alzheimer’s disease (AD) is a neurodegenerative disorder of gradual progression that leads to cognitive decline and multiple pathological processes. A key issue in the treatment of AD is the complexity of the disease mechanism, as a result of which single-target drugs fail to show efficacy. Multitarget-directed ligands (MTDLs) appear to be a promising way to treat such diseases as they modulate several disease-related targets. Indole–chalcone hybrids are of particular interest due to the presence of two pharmacophores with complementary properties. This review discusses the possibilities of using hybrid molecules of indole and chalcone for the treatment of AD. The literature data concerning the treatment of AD with indole derivatives, chalcone-based drugs, and directly related indole–chalcone hybrids were analysed. Particular attention was drawn to the study of the structure–activity relationship, synthesis and methods of study of pharmacological activity of derivatives of these two heterosystems, such as inhibition of cholinesterase enzyme, monoamine oxidase, formation of aggregates of amyloid-β peptide and the reduction of oxidative stress and neuroinflammation. Based on the analysis, it was found that some indole–chalcone derivatives showed good monoamine oxidase-B and butyrylcholinesterase inhibitory activities but were weak in terms of acetylcholinesterase inhibition. Data on the activity of these hybrids against other disease mechanisms are lacking. However, the search for optimal ligands worthy of further detailed study is still relevant. Possible problems in this field include the lack of data on the ability to penetrate the blood–brain barrier, low overall efficacy and insufficient study of the interaction of such molecules with various disease-related targets. Targeted optimisation of promising leads, increased multitarget activity and specificity, and comprehensive preclinical study of their pharmacological characteristics will allow further exploration of these hybrid molecules.



Keywords

Alzheimer's disease, multitarget-directed ligands, indole, chalcone, cholinesterase, monoamine oxidase, amyloid-β, neuroinflammation



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