Chalcone and its analogs: Therapeutic and diagnostic applications in Alzheimer’s disease

Thapa, Pritam; Upadhyay, Sunil P.; Suo, William Z.; Singh, Vikas; Gurung, Prajwal; Lee, Eung Seok; Sharma, Ram; Sharma, Mukut

doi:10.1016/j.bioorg.2021.104681

Cited by 83 publications

(50 citation statements)

References 256 publications

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“…However, even with lower differences, the highest concentration corresponded to EF from plants in region A. Chalcones are polyphenols are structured as α,β-unsaturated aromatic ketones and can be found in various plants. They have been targeted in various studies that provide data about their potential in various therapeutic purposes, attributing bioactivities to them, such as helpfulness regarding oncology, infections and even in neurodegenerative diseases, including Alzheimer's [29]. For the latter, the antioxidant and anti-inflammatory effects are also very important, and the data obtained with the present extract was found to be promising for some of these applications, as shown below.…”

Section: Hplc/dadmentioning

confidence: 82%

Special Bioactivities of Phenolics from Acacia dealbata L. with Potential for Dementia, Diabetes and Antimicrobial Treatments

et al. 2022

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Some diseases still need better therapeutic approaches, including the prevention of development. Natural resources are investigated with this purpose; among them, we decided to use an invasive plant as a main strategy. This will help in two ways: screening new compounds in flowers prevents the plant from causing widespread damage by controlling the dissemination and also obtains crude material for further applications. In the present study, flower extracts from Acacia dealbata Link harvested in Portugal were studied during three stages of flowering. Phenolic compounds were evaluated using HPLC/DAD and the total phenolics as the total flavonoids content was determined. The bioactivities screened were antioxidant potential, inhibitory activities of some enzymes (acetylcholinesterase, lipase and α-glucosidase) and, to complete the screening, the inhibition of microbial growth was determined against Gram-negative and Gram-positive bacteria, as well as for yeasts. The data obtained suggested that the hydroethanolic extracts gave good results for all these biological activities and varied according to the maturation status of the flowers, with the early stage being the most active, which can be related to the chalcones content. This new approach will lead to the possible control of the invasive plant and also future perspective research for therapeutic purposes.

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Section: Hplc/dadmentioning

confidence: 82%

Special Bioactivities of Phenolics from Acacia dealbata L. with Potential for Dementia, Diabetes and Antimicrobial Treatments

et al. 2022

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“…In order to consider which classes are most suitable, based on the benefits and drawbacks, certain structural features of each class will be of great importance. Using chalcones as an example, it is believed that besides economical and cost-effective production, small molecular size and flexibility for modifications to improve lipophilicity necessary for blood-brain barrier permeability are important to consider for a preferred potential therapeutic candidate for AD [ 118 ]. Terpenoids are able to inhibit cholinesterases in different ways.…”

Section: Discussionmentioning

confidence: 99%

Non-Alkaloid Cholinesterase Inhibitory Compounds from Natural Sources

et al. 2021

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Alzheimer’s disease (AD) is a severe neurodegenerative disorder of different brain regions accompanied by distresses and affecting more than 25 million people in the world. This progressive brain deterioration affects the central nervous system and has negative impacts on a patient’s daily activities such as memory impairment. The most important challenge concerning AD is the development of new drugs for long-term treatment or prevention, with lesser side effects and greater efficiency as cholinesterases inhibitors and the ability to remove amyloid-beta(Aβ) deposits and other related AD neuropathologies. Natural sources provide promising alternatives to synthetic cholinesterase inhibitors and many have been reported for alkaloids while neglecting other classes with potential cholinesterase inhibition. This review summarizes information about the therapeutic potential of small natural molecules from medicinal herbs, belonging to terpenoids, coumarins, and phenolic compounds, and others, which have gained special attention due to their specific modes of action and their advantages of low toxicity and high efficiency in the treatment of AD. Some show superior drug-like features in comparison to synthetic cholinesterase inhibitors. We expect that the listed phytoconstituents in this review will serve as promising tools and chemical scaffolds for the discovery of new potent therapeutic leads for the amelioration and treatment of Alzheimer’s disease.

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“…Notably, the identified framework is present in some of the already reported Tau-based drug candidates currently undergoing clinical trials (e.g., xalsalate and curcumin) ( Figure S3 ) [ 69 , 70 ], as well as in the natural compounds xanthohumol and licochalcone A that act as Tau aggregation inhibitors [ 70 , 71 ] ( Figure S3 ). The latter chemotype is currently under evaluation on several targets related to neurodegenerative diseases, including monoaminoxidase B, αβ-amyloid and α-sinuclein [ 72 , 73 , 74 ].…”

Section: Resultsmentioning

confidence: 99%

Chemoinformatics Analyses of Tau Ligands Reveal Key Molecular Requirements for the Identification of Potential Drug Candidates against Tauopathies

2021

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Tau is a highly soluble protein mainly localized at a cytoplasmic level in the neuronal cells, which plays a crucial role in the regulation of microtubule dynamic stability. Recent studies have demonstrated that several factors, such as hyperphosphorylation or alterations of Tau metabolism, may contribute to the pathological accumulation of protein aggregates, which can result in neuronal death and the onset of a number of neurological disorders called Tauopathies. At present, there are no available therapeutic remedies able to reduce Tau aggregation, nor are there any structural clues or guidelines for the rational identification of compounds preventing the accumulation of protein aggregates. To help identify the structural properties required for anti-Tau aggregation activity, we performed extensive chemoinformatics analyses on a dataset of Tau ligands reported in ChEMBL. The performed analyses allowed us to identify a set of molecular properties that are in common between known active ligands. Moreover, extensive analyses of the fragment composition of reported ligands led to the identification of chemical moieties and fragment combinations prevalent in the more active compounds. Interestingly, many of these fragments were arranged in recurring frameworks, some of which were clearly present in compounds currently under clinical investigation. This work represents the first in-depth chemoinformatics study of the molecular properties, constituting fragments and similarity profiles, of known Tau aggregation inhibitors. The datasets of compounds employed for the analyses, the identified molecular fragments and their combinations are made publicly available as supplementary material.

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Chalcone and its analogs: Therapeutic and diagnostic applications in Alzheimer’s disease

Cited by 83 publications

References 256 publications

Special Bioactivities of Phenolics from Acacia dealbata L. with Potential for Dementia, Diabetes and Antimicrobial Treatments

Special Bioactivities of Phenolics from Acacia dealbata L. with Potential for Dementia, Diabetes and Antimicrobial Treatments

Non-Alkaloid Cholinesterase Inhibitory Compounds from Natural Sources

Chemoinformatics Analyses of Tau Ligands Reveal Key Molecular Requirements for the Identification of Potential Drug Candidates against Tauopathies

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