Alzheimer's Disease (AD), affecting a large population worldwide, is characterized by the old population's loss of memory and learning ability. Cholinergic deficiency is associated with AD, and various cholinesterase inhibitors have been developed to treat AD, including naturally-derived inhibitors, synthetic analogs, and hybrids. Acetylcholinesterase (AChE) has obtained a renewed interest as a therapeutic target in Alzheimer's disease (AD) due to increased neural cells' function by increasing the concentration of acetylcholine. In this review, we reported the recent development of novel heterocyclic compounds such as coumarin-benzotriazole hybrids, carbazole derivatives, tacrine conjugates, N-benzyl-piperidine-aryl-acyl hydrazones hybrid, spiropyrazoline derivatives, coumarin-dithiocarbamate hybrids, etc., as AChE inhibitors for the treatment of Alzheimer disease. All the bioactive compounds show an effect on different cells and interact simultaneously with the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE with a narrow range of IC50 values from 0.4 nm to 88.21 µm using Ellman’s in vitro AChE assay method and show high BBB permeability in-vitro. In addition, the in-vitro fluorescence assay study using Amplex Red assay kits revealed that all the compounds could inhibit self-induced β-amyloid (Aβ) aggregation with the highest inhibition range from 31.4 to 82%. Furthermore, most of the compounds show a low toxicity profile during in vivo studies. The results suggest that all the compounds constitute promising leads for the AChE targeted approach for Alzheimer’s disease.
: Quinoxaline is a versatile heterocyclic moiety that possesses a wide range of biological activities. Therefore, many researchers have been performing the synthesis of quinoxaline derivatives on a daily basis. In addition, high demands for their synthesis often result in an increased generation of different waste chemicals. However, to minimize the utilization and generation of toxic organic substances, the present review focuses on the various green synthetic approaches for the synthesis of quinoxaline and its derivatives. Moreover, due to the quick manufacturing of novel medications using a quinoxaline scaffold, multiple study reports are published in a short period of time. Therefore, to fully comprehend the current state of the quinoxaline scaffold in medicinal chemistry, it is necessary to combine recent findings with previous understanding. Besides, compared to conventional methods, these green methods minimize the use and generation of harmful chemicals and improve reaction efficiency in terms of product yields, purity, energy consumption, and post-synthetic procedures. Therefore, in this review, we have attempted to shed light on various green synthetic strategies leading to the synthesis of quinoxaline scaffold and its derivatives, such as ultrasound irradiation, microwave irradiation, grindstone technique, environmentally benign solvents/catalysts based, and reactant immobilized on a solid support, etc.
Coumarin and its derivatives are privileged heterocyclic motifs and important building blocks for developing the biologically active compound due to its significant role in the development of new drugs. As a result, many methodologies have been developed to synthesize this important class of compounds. However, some methods are associated with toxic and corrosive catalysts, longer reaction time, poor yield, less purity, and by-products along with the desired product. In order to minimize the utilization and generation of toxic organic substances, green synthetic methods are applied in this manner. Green chemistry methods cover a wide range of methods, including the application of ultrasound and microwaves, ionic liquids and deep eutectic solvents, solvent-free and catalyst-free synthesis, and mechanosynthesis. These green synthetic methods have successfully performed all typical condensation reactions for coumarin synthesis like Knoevenagel, Perkin, Kostanecki-Robinson, Pechmann, and Reformatsky reactions. Compared to conventional methods, these methods not only minimize the use and generation of harmful chemicals but also improve reaction efficiency in terms of product yields, purity, energy consumption, and post-synthetic procedures. Due to the implication of coumarin (2-oxo-2H-1-benzopyran) backbone as a biologically active ubiquitous fragment and the recent demands of reducing toxic solvents, catalysts, and energy consumption, this review summarized various green synthetic methods for coumarin synthesis. Moreover, researchers working on this coumarin scaffold synthesis can find handy information from this review on the green synthetic approaches to their synthesis.
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