Synthesis and biological evaluation of benzimidazoles/1,3,5-triazine-2,4-diamine hybrid compounds: a new class of multifunctional alzheimer targeting agents

Karimian, Somaye; Shekouhy, Mohsen; Pirhadi, somaye; Iraji, Aida; Attarroshan, Mahshid; Edraki, Najmeh; Khoshneviszadeh, Mehdi

doi:10.1039/d2nj00371f

Cited by 7 publications

(4 citation statements)

References 47 publications

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“…[29] 1,3,5-Triazine hybrid compounds have been developed as multi-target ligands against Alzheimer's disease. [30] Some of the 1,3,5-triazine derivatives were designed and synthesized as AChE inhibitors. Those compounds possessed potent AChE inhibitory activities.…”

Section: Introductionmentioning

confidence: 99%

“…Numerous 1.3,5‐triazine‐containing molecules are capable of modulating single as well as multiple pathological factors involved in AD due to the potential for multiple biological effects of 1.3,5‐triazine [29] . 1,3,5‐Triazine hybrid compounds have been developed as multi‐target ligands against Alzheimer's disease [30] . Some of the 1,3,5‐triazine derivatives were designed and synthesized as AChE inhibitors.…”

Section: Introductionmentioning

confidence: 99%

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Design, Synthesis and Anticholinesterase Activity of Coumarin‐1,3,5‐triazine Derivatives

Zhang,

Wang,

Zou

et al. 2024

ChemistrySelect

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A series of coumarin‐1,3,5‐triazine derivatives were designed, synthesized and evaluated as acetylcholinesterase inhibitors. The structures of those compounds were characterized by IR, NMR, HRMS, HPLC, and X‐ray. The structures of those coumarin‐1,3,5‐triazine derivatives are the mixtures of two geometric isomers. The 1H‐NMR of compound 3 g without coumarin structure and its hydrochloride and single crystal structure of compound 3 g were studied to prove the coumarin‐1,3,5‐triazine derivatives are the mixtures of two geometric isomers. The acetylcholinesterase and butyrylcholinesterase inhibitory activities of the synthesized compounds were determinated by Ellman's method. The results showed that all the compounds could inhibit acetylcholinesterase selectively. Among them, compound 3 b was found to have the strongest inhibitory effect on acetylcholinesterase with an IC50 value of 0.018 μM, which was closest to the IC50 of the positive control donepezil (IC50=0.016 μM). Enzyme kinetic studies indicate that this compound inhibited acetylcholinesterase with a mixed mode. Molecular docking, molecular dynamics simulation study and binding free energy calculation experiments demonstrated that compound 3 b could stably interact with key amino acids in the catalytically active site and the peripheral anion site of acetylcholinesterase. According to the results, compound 3 b demonstrates promising potential as acetylcholinesterase inhibitors for the treatment of Alzheimer's disease.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Anticholinesterase Activity of Coumarin‐1,3,5‐triazine Derivatives

Zhang,

Wang,

Zou

et al. 2024

ChemistrySelect

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show abstract

Section: Introductionmentioning

confidence: 99%

“…In addition to all these activities, triazines, both 1,2,4-isomers [15,16] and 1,3,5-isomers [17][18][19], were found to exhibit the ability to inhibit the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1), see Figure 1. In addition to all these activities, triazines, both 1,2,4-isomers [15,16] and 1,3,5-isomers [17][18][19], were found to exhibit the ability to inhibit the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1), see Figure 1. BACE1 (otherwise known as β-secretase) [20,21] is an enzyme that, in its subsequent interaction with γ-secretase, cleaves the amyloid precursor protein into the insoluble Aβ42 isoform of the amyloid-β (Aβ) protein (the so-called "amyloidogenic pathway") [22].…”

Section: Introductionmentioning

confidence: 99%

Trisubstituted 1,3,5-Triazines and Their Effect on BACE1

Majerova,

Gerhardtova,

Havrankova

et al. 2023

Ecsoc 2023

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New benzimidazole–indole–amide derivatives as potent α‐glucosidase and acetylcholinesterase inhibitors

Naimi,

Karimian,

Dastyafteh

et al. 2024

Archiv der Pharmazie

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New derivatives 6a–m with benzimidazole–indole–amide scaffold were developed, synthesized, and assessed for potential inhibitory effects on α‐glucosidase and acetylcholinesterase (AChE). These compounds were synthesized by various amine derivatives. With the exception of two compounds, the α‐glucosidase inhibitory activities of the title derivatives were more than that of the positive control acarbose. Moreover, the anti‐AChE activity of these compounds, with the exception of one compound, was better than that of tacrine (standard inhibitor). The most potent compound against α‐glucosidase was 3‐methylphenyl derivative 6i and the most potent compound against AChE was 3,4‐dimethoxyphenethyl derivative 6m. All the synthesized compounds were placed in the active sites of α‐glucosidase and AChE by in silico docking method and the obtained binding energies were approximately in agreement with the in vitro observed data. Interaction modes of the most potent compounds 6i and 6m demonstrated that these compounds interacted with important residues of their target enzymes. Molecular dynamics simulation was conducted specifically on compound 6i in complex with α‐glucosidase to obtain deeper insights into the behavior of this molecule. Furthermore, in silico pharmacokinetic and toxicity studies on the most potent compound predicted that these compounds have good profiles in terms of oral absorption and toxicity.

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Synthesis and biological evaluation of benzimidazoles/1,3,5-triazine-2,4-diamine hybrid compounds: a new class of multifunctional alzheimer targeting agents

Abstract: Twelve novel benzimidazole/1,3,5-triazine-2,4-diamine hybrids were synthesized and biologically studied as multifunctional Alzheimer-controlling agents.

Cited by 7 publications

References 47 publications

Design, Synthesis and Anticholinesterase Activity of Coumarin‐1,3,5‐triazine Derivatives

Design, Synthesis and Anticholinesterase Activity of Coumarin‐1,3,5‐triazine Derivatives

Trisubstituted 1,3,5-Triazines and Their Effect on BACE1

New benzimidazole–indole–amide derivatives as potent α‐glucosidase and acetylcholinesterase inhibitors

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