Novel 3-phenylcoumarin–lipoic acid conjugates as multi-functional agents for potential treatment of Alzheimer's disease

Jalili‐Baleh, Leili; Nadri, Hamid; Forootanfar, Hamid; Samzadeh‐Kermani, Alireza; Küçükkılınç, Tuba Tüylü; Ayazgök, Beyza; Rahimifard, Mahban; Baeeri, Maryam; Doostmohammadi, Mohsen; Firoozpour, Loghman; Bukhari, Syed Nasir Abbas; Abdollahi, Mohammad; Ganjali, Mohammad Reza; Emami, Saeed; Khoobi, Mehdi; Foroumadi, Alireza

doi:10.1016/j.bioorg.2018.04.030

Cited by 42 publications

(21 citation statements)

References 51 publications

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“…14), was synthesised and identified as the most active derivative with IC 50 values of 7.3 µM for AChE and 68.6 µM for butyrylcholinesterase (BuChE). 142 The steadystate inhibition assay showed that high concentrations of derivative 113 showed increase inhibitory potency.…”

Section: 23-triazoles As Alzheimer's Disease Agentsmentioning

confidence: 99%

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

Bozorov

Zhao

Aisa

2019

Bioorganic & Medicinal Chemistry

618

289

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A B S T R A C TThe 1,2,3-triazole ring is a major pharmacophore system among nitrogen-containing heterocycles. These fivemembered heterocyclic motifs with three nitrogen heteroatoms can be prepared easily using 'click' chemistry with copper-or ruthenium-catalysed azide-alkyne cycloaddition reactions. Recently, the 'linker' property of 1,2,3-triazoles was demonstrated, and a novel class of 1,2,3-triazole-containing hybrids and conjugates was synthesised and evaluated as lead compounds for diverse biological targets. These lead compounds have been demonstrated as anticancer, antimicrobial, anti-tubercular, antiviral, antidiabetic, antimalarial, anti-leishmanial, and neuroprotective agents. The present review summarises advances in lead compounds of 1,2,3-triazolecontaining hybrids, conjugates, and their related heterocycles in medicinal chemistry published in 2018. This review will be useful to scientists in research fields of organic synthesis, medicinal chemistry, phytochemistry, and pharmacology. Chemistry: synthesis and properties of the 1,2,3-triazolesThe general synthetic route of 1,2,3-triazoles using click chemistry is described in Scheme 1A. The most popular route to 1,2,3-triazoles is Cu(I)-catalysed Huisgen 1,3-dipolar cycloaddition, which is the https://doi.

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Section: 23-triazoles As Alzheimer's Disease Agentsmentioning

confidence: 99%

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

Bozorov

Zhao

Aisa

2019

Bioorganic & Medicinal Chemistry

618

289

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“…Coumarin structures as active natural compounds may simultaneously possess anti-oxidative [ 2 , 26 ], neuroprotective [ 27 ] anti-ChE [ 20 ] and anti-Aβ aggregative properties [ 28 , 29 ]. Coumarins pharmacophore owing to the presence of polar elements in the structure (Fig.…”

Section: Resultsmentioning

confidence: 99%

Design and synthesis of multi-target directed 1,2,3-triazole-dimethylaminoacryloyl-chromenone derivatives with potential use in Alzheimer's disease

et al. 2020

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To discover multifunctional agents for the treatment of Alzheimer's disease (AD), a new series of 1,2,3-triazole-chromenone derivatives were designed and synthesized based on the multi target-directed ligands approach. The in vitro biological activities included acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition as well as anti-Aβ aggregation, neuroprotective effects, and metal-chelating properties. The results indicated a highly selective BuChE inhibitory activity with an IC50 value of 21.71 μM for compound 10h as the most potent compound. Besides, compound 10h could inhibit self-induced Aβ1–42 aggregation and AChE-induced Aβ aggregation with 32.6% and 29.4% inhibition values, respectively. The Lineweaver–Burk plot and molecular modeling study showed that compound 10h targeted both the catalytic active site (CAS) and peripheral anionic site (PAS) of BuChE. It should be noted that compound 10h was able to chelate biometals. Thus, the designed scaffold could be considered as multifunctional agents in AD drug discovery developments.

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“…This compound was the most potent AChEI (IC 50 = 7.3 µM) and displayed the highest antioxidant activity in neuronal PC12 cells at the 50 µM (43.7%), aside of a good biometal-chelator for Mg 2+ , Ca 2+ , Al 3+ , Cu 2+ , Fe 2+ and Zn 2+ . Furthermore, this compound showed 52.6% (at 10 µM) of neuroprotection in human neuroblastoma cells [ 126 ].…”

Section: Molecular Hybrids Designed As Prototypes Of Drug Candidates mentioning

confidence: 99%

Molecular Hybridization as a Tool in the Design of Multi-target Directed Drug Candidates for Neurodegenerative Diseases

Gontijo

Viegas

Ortiz

et al. 2020

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Neurodegenerative Diseases (NDs) are progressive multifactorial neurological pathologies related to neuronal impairment and functional loss from different brain regions. Currently, no effective treatments are available for any NDs, and this lack of efficacy has been attributed to the multitude of interconnected factors involved in their pathophysiology. In the last two decades, a new approach for the rational design of new drug candidates, also called multitarget-directed ligands (MTDLs) strategy, has emerged and has been used in the design and for the development of a variety of hybrid compounds capable to act simultaneously in diverse biological targets. Based on the polypharmacology concept, this new paradigm has been thought as a more secure and effective way for modulating concomitantly two or more biochemical pathways responsible for the onset and progress of NDs, trying to overcome low therapeutical effectiveness. As a complement to our previous review article (Curr. Med. Chem. 2007, 14 (17), 1829-1852. https://doi.org/10.2174/092986707781058805), herein we aimed to cover the period from 2008 to 2019 and highlight the most recent advances of the exploitation of Molecular Hybridization (MH) as a tool in the rational design of innovative multifunctional drug candidate prototypes for the treatment of NDs, specially focused on AD, PD, HD and ALS.

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Novel 3-phenylcoumarin–lipoic acid conjugates as multi-functional agents for potential treatment of Alzheimer's disease

Cited by 42 publications

References 51 publications

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

Design and synthesis of multi-target directed 1,2,3-triazole-dimethylaminoacryloyl-chromenone derivatives with potential use in Alzheimer's disease

Molecular Hybridization as a Tool in the Design of Multi-target Directed Drug Candidates for Neurodegenerative Diseases

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