Coumarin Derivatives in Pharmacotherapy of Alzheimer´s Disease

Title:Coumarin Derivatives in Pharmacotherapy of Alzheimer´s Disease

Volume: 21 Issue: 7

Author(s): Slavka Hamulakova, Maria Kozurkova and Kamil Kuca

Affiliation:

Keywords: Coumarin, Alzheimer´s Disease, acetylcholinesterase inhibitor, Aβ aggregation, bis-coumarin dimers, tacrine-coumarin heterodimers, monoamine oxidases.

Abstract: Coumarins are naturally occurring phytochemicals with heterocyclic structures which display a wide range of biological activities against neurological diseases such as Alzheimer´s disease (AD). This study reviews recent research into the design, synthesis and pharmacological profile of several series of synthetic coumarin ligands with clearcholinesterase, and assesses the monoamino oxidases (MAO-A and MAO-B) inhibitory activity, Aβ anti-aggregation potency and antioxidant properties reported for these novel derivatives. Our attention is focused on a comparison of the neuroprotective effects of these coumarin derivatives in terms of their potential as mono-, homo- and heterodimers as agents in the treatment of AD. The monocoumarin derivatives 13a & 13b with benzyl pyridinium group showed outstanding levels of acetylcholinesterase inhibitory activity (IC₅₀ = 0.11, 0.16 nM). Bis-coumarin ligands showed high levels of inhibitory activity and selectivity for MAO-A. Tacrinecoumarin heterodimer 21b was the most active inhibitor of hBChE (IC₅₀ = 38 pM).

Cite this article as:

Hamulakova Slavka, Kozurkova Maria and Kuca Kamil, Coumarin Derivatives in Pharmacotherapy of Alzheimer´s Disease, Current Organic Chemistry 2017; 21 (7) . https://dx.doi.org/10.2174/1385272820666160601155411