Coumarins are a large class of compounds that display a range of interesting biological properties, being considered privileged structures because of the ability of their 2H-chromen-2-one nuclei to bind to multiple pharmacological targets. We hypothesized that the linkage of a second pharmacophore nucleus to the 2H-chromen-2-one core, the 1,2,3-triazole moiety, would entail more selective and pharmacologically active coumarins. Therefore, we describe the synthesis of fourteen 4-methylcoumarins/1,4-substituted 1,2,3-triazole conjugates, which were predicted by in silico methods to inhibit acetylcholinesterase (AChE) and proved to be moderate in vitro inhibitors of this enzyme. Molecular docking simulations suggest that the most active of these compounds has a putative binding mode similar to donepezil, both occupying the peripheral anionic site of AChE, which is associated with the secondary noncholinergic functions of the enzyme. This highlights the potential of this series for further optimization in the search of new coumarins for the treatment of Alzheimer's disease.
The complexity of Chagas disease is still a challenge in endemic regions and an emergent public health problem
in non-endemic countries. The causative agent of this neglected tropical disease, Trypanosoma cruzi, is mainly transmitted
by triatomine vectors and possesses multiple epidemiologically important strains. Current chemotherapeutics are outdated
and their limited efficacy is one of the major reasons for treatment discontinuation. In this context, it is urgent the
development of novel, safe and economically accessible antichagasic drugs. Various classes of heterocycles and natural
compounds have been described as potential antichagasic scaffolds, and coumarins are no exception. These versatile
compounds have a wide spectrum of biological activities, and numerous natural and synthetic coumarins have been reported
with antichagasic potential. The aim of this review is to discuss the available literature between 2001 and 2020 regarding
natural and synthetic coumarins with anti-Trypanosoma cruzi activity. Moreover, some of the studies herein comprised are
dedicated to the potential of coumarins to inhibit promising targets in Trypanosoma cruzi.
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