Multi-target inhibitors against Alzheimer disease derived from 3-hydrazinyl 1,2,4-triazine scaffold containing pendant phenoxy methyl-1,2,3-triazole: Design, synthesis and biological evaluation

Yazdani, Mehdi; Edraki, Najmeh; Badri, Rashid; Khoshneviszadeh, Mahsima; Firuzi, Omidreza

doi:10.1016/j.bioorg.2018.11.038

Cited by 61 publications

(29 citation statements)

References 26 publications

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“…The absorbance (A570 nm) was measured using a Bio-Rad microplate reader (Model 680, Bio-Rad). The details were reported in our previous work [ 33 , 46 ].…”

Section: Methodsmentioning

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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“…The absorbance (A570 nm) was measured using a Bio-Rad microplate reader (Model 680, Bio-Rad). The details were reported in our previous work [ 33 , 46 ].…”

Section: Methodsmentioning

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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“…As additional modifications to the triazine core, compounds with general structure 48 ( Figure 15) were reported [112]. Here, the introduction of the aryl phenoxymethyl-1,2,3-triazole moiety added further potential to display metal-chelating and antioxidant effects.…”

Section: Bace-1 Inhibitors and Their Combinations Intomentioning

confidence: 99%

Multitarget Therapeutic Strategies for Alzheimer’s Disease: Review on Emerging Target Combinations

Maramai

Benchekroun

Gabr

et al. 2020

BioMed Research International

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Neurodegenerative diseases represent nowadays one of the major health problems. Despite the efforts made to unveil the mechanism leading to neurodegeneration, it is still not entirely clear what triggers this phenomenon and what allows its progression. Nevertheless, it is accepted that neurodegeneration is a consequence of several detrimental processes, such as protein aggregation, oxidative stress, and neuroinflammation, finally resulting in the loss of neuronal functions. Starting from these evidences, there has been a wide search for novel agents able to address more than a single event at the same time, the so-called multitarget-directed ligands (MTDLs). These compounds originated from the combination of different pharmacophoric elements which endowed them with the ability to interfere with different enzymatic and/or receptor systems, or to exert neuroprotective effects by modulating proteins and metal homeostasis. MTDLs have been the focus of the latest strategies to discover a new treatment for Alzheimer’s disease (AD), which is considered the most common form of dementia characterized by neurodegeneration and cognitive dysfunctions. This review is aimed at collecting the latest and most interesting target combinations for the treatment of AD, with a detailed discussion on new agents with favorable in vitro properties and on optimized structures that have already been assessed in vivo in animal models of dementia.

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“…The 4-hydroxy-3-methoxybenzohydrazide intermediate (3, Scheme 1) were prepared using commercially available methyl 4-hydroxy-3-methoxybenzoate (1, Scheme 1) and hydrazine hydrate (2, Scheme 1) in refluxing ethanol in the presence of catalytic amounts of acetic acid under simple nucleophilic substitution reaction and completion of the reaction was monitored by TLC to give compound [20]. The treatment of 3 with an appropriate aldehyde in the presence of acetic acid in 2-propanol yielded the desired final products 4a-k (80-92%) [21]. Structural determination and signal assignments of the final compounds were accomplished by the application of IR, MASS and NMR experiments.…”

Section: Chemistrymentioning

confidence: 99%

Synthesis, biological evaluation and molecular docking analysis of vaniline–benzylidenehydrazine hybrids as potent tyrosinase inhibitors

et al. 2020

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In this work, 11 novel compounds based on vaniline and benzylidenehydrazine structure were synthesized with various substituents on phenyl aromatic ring of the molecule and evaluated as tyrosinase inhibitors. These new derivatives showed significant anti-tyrosinase activities, among which 4i demonstrated to be the most potent compound, with IC 50 values of 1.58 µM. The structure-activity relationship study of the novel constructed analogs was fully discussed. Kinetic study of compound 4i showed uncompetitive inhibition towards tyrosinase. Furthermore, the high potency of 4i was supported theoretically by molecular docking evaluations.

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Multi-target inhibitors against Alzheimer disease derived from 3-hydrazinyl 1,2,4-triazine scaffold containing pendant phenoxy methyl-1,2,3-triazole: Design, synthesis and biological evaluation

Cited by 61 publications

References 26 publications

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

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

Multitarget Therapeutic Strategies for Alzheimer’s Disease: Review on Emerging Target Combinations

Synthesis, biological evaluation and molecular docking analysis of vaniline–benzylidenehydrazine hybrids as potent tyrosinase inhibitors

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