Synthesis of 4-substituted benzyl-2-triazole-linked-tryptamine-paeonol derivatives and evaluation of their selective inhibitions against butyrylcholinesterase and monoamine oxidase-B

Oh, Jong Min; Kang, Yang Jun; Hwang, Ji Hyun; Park, Jeong-Ho; Shin, Woong-Hee; Mun, Seul-Ki; Lee, Jong Uk; Yee, Sung‐Tae; Kim, Hoon

doi:10.1016/j.ijbiomac.2022.07.178

Cited by 17 publications

(12 citation statements)

References 53 publications

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“…Comparing the in-silico binding energies, compound 7 showed higher binding energy than 8 against BuChE (−13.75 vs. −11.29 kcal/mol); however, compound 8 has higher binding energy against MAO-B than MAO-A (−11.31 vs. −6.72 kcal/mol). The derivatives were slightly cytotoxic against normal cells (MDCK) and human neuroblastoma cells (SH-SY5Y) [ 63 ].…”

Section: Conjugates Of 123-triazole As Potential Ache and Buche Inhib...mentioning

confidence: 99%

An Overview of 1,2,3-triazole-Containing Hybrids and Their Potential Anticholinesterase Activities

Khan¹,

Akhtar²,

Gogoi

et al. 2023

Pharmaceuticals

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Acetylcholine (ACh) neurotransmitter of the cholinergic system in the brain is involved in learning, memory, stress responses, and cognitive functioning. It is hydrolyzed into choline and acetic acid by two key cholinesterase enzymes, viz., acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). A loss or degeneration of cholinergic neurons that leads to a reduction in ACh levels is considered a significant contributing factor in the development of neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD). Numerous studies have shown that cholinesterase inhibitors can raise the level of ACh and, therefore, enhance people’s quality of life, and, at the very least, it can temporarily lessen the symptoms of NDs. 1,2,3-triazole, a five-membered heterocyclic ring, is a privileged moiety, that is, a central scaffold, and is capable of interacting with a variety of receptors and enzymes to exhibit a broad range of important biological activities. Recently, it has been clubbed with other pharmacophoric fragments/molecules in hope of obtaining potent and selective AChE and/or BuChE inhibitors. The present updated review succinctly summarizes the different synthetic strategies used to synthesize the 1,2,3-triazole moiety. It also highlights the anticholinesterase potential of various 1,2,3-triazole di/trihybrids reported in the past seven years (2015-2022), including a rationale for hybridization and with an emphasis on their structural features for the development and optimization of cholinesterase inhibitors to treat NDs.

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Section: Conjugates Of 123-triazole As Potential Ache and Buche Inhib...mentioning

confidence: 99%

An Overview of 1,2,3-triazole-Containing Hybrids and Their Potential Anticholinesterase Activities

Khan¹,

Akhtar²,

Gogoi

et al. 2023

Pharmaceuticals

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“…Residual activity was assayed after the addition of the 10 μM inhibitor as an initial screening step; IC 50 values were then determined for potential compounds with residual activity of less than 50% using residual activity curves obtained by GraphPad Prism software 5 (San Diego, CA) . By dividing the IC 50 of MAO-A with that of MAO-B, the selectivity index (SI) value of MAO-B was determined .…”

Section: Methodsmentioning

confidence: 99%

Development of a New Class of Monoamine Oxidase-B Inhibitors by Fine-Tuning the Halogens on the Acylhydrazones

Jayan,

Lee,

Kumar

et al. 2023

ACS Omega

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A total of 14 acyl hydrazine derivatives ( ACH1–ACH14 ) were developed and examined for their ability to block monoamine oxidase (MAO). Thirteen analogues showed stronger inhibition potency against MAO-B than MAO-A. With a half-maximum inhibitory concentration of 0.14 μM, ACH10 demonstrated the strongest inhibitory activity against MAO-B, followed by ACH14 , ACH13 , ACH8 , and ACH3 (IC 50 = 0.15, 0.18, 0.20, and 0.22 μM, respectively). Structure–activity relationships suggested that the inhibition effect on MAO-B resulted from the combination of halogen substituents of the A- and/or B-rings. This series concluded that when –F was substituted to the B-ring, MAO-B inhibitory activities were high, except for ACH6 . In the inhibition kinetics study, the compounds ACH10 and ACH14 were identified as competitive inhibitors, with K i values of 0.097 ± 0.0021 and 0.10 ± 0.038 μM, respectively. In a reversibility experiment using the dialysis methods, ACH10 and ACH14 showed effective recoveries of MAO-B inhibition as much as lazabemide, a reversible reference. These experiments proposed that ACH10 and ACH14 were efficient, reversible competitive MAO-B inhibitors. In addition, the lead molecules showed good blood–brain barrier permeation with the PAMPA method. The molecular docking and molecular dynamics simulation study confirmed that the hit compound ACH10 can form a stable protein–ligand complex by forming a hydrogen bond with the NH atom in the hydrazide group of the compound.

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“…After first determination at 10 μM, the IC 50 values of the compounds were calculated by using GraphPad Prism software 5 [41]. The selectivity index (SI) values of compounds were calculated by (IC 50 of MAO-A or AChE)/(IC 50 of MAO-B or BChE) [42].…”

Section: Enzyme Kineticsmentioning

confidence: 99%

“…The selectivity index (SI) values of compounds were calculated by (IC 50 of MAO-A or AChE)/(IC 50 of MAO-B or BChE) [42]. The inhibition types of compound 1 for MAO-B and BChE were determined at five different substrate concentrations [35,43], and three inhibitor concentrations of ~0.5, 1.0, and 2.0 times of its IC 50 values [41]. The inhibition patterns and K i values were determined by comparing the Lineweaver-Burk plots and their secondary plots, respectively [38].…”

Section: Enzyme Kineticsmentioning

confidence: 99%

3-Phenethyl-2-phenylquinazolin-4(3H)-one isolated from marine-derived Acremonium sp. CNQ-049 as a dual- functional inhibitor of monoamine oxidases-B and butyrylcholinesterase

Hillman

Nam

et al. 2023

JABC

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Isolation of the culture broth of a marine-derived Acremonium sp. CNQ-049 guided by HPLC-UV yielded compound 1 (3-phenethyl-2-phenylquinazolin-4(3H)-one), and its inhibitory activities against monoamine oxidases (MAOs), cholinesterases (ChEs), and β-secretase 1 (BACE1) were evaluated. Compound 1 was an effective selective MAO-B inhibitor with an IC 50 value of 9.39 μM and a selectivity index (SI) value of 4.26 versus MAO-A. In addition, compound 1 showed a potent selective butyrylcholinesterase (BChE) inhibition with an IC 50 value of 7.99 μM and an SI value of 5.01 versus acetylcholinesterase (AChE). However, compound 1 showed weak inhibitions against MAO-A, AChE, and BACE1. The K i value of compound 1 for MAO-B was 5.22±1.73 μM with competitive inhibition, and the K i value of compound 1 for BChE was 3.00±1.81 μM with mixed-type inhibition. Inhibitions of MAO-B and BChE by compound 1 were recovered by dialysis experiments. These results suggest that compound 1 is a dual-functional reversible inhibitor of MAO-B and BChE, that can be used as a treatment agent for neurological disorders.

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Synthesis of 4-substituted benzyl-2-triazole-linked-tryptamine-paeonol derivatives and evaluation of their selective inhibitions against butyrylcholinesterase and monoamine oxidase-B

Cited by 17 publications

References 53 publications

An Overview of 1,2,3-triazole-Containing Hybrids and Their Potential Anticholinesterase Activities

An Overview of 1,2,3-triazole-Containing Hybrids and Their Potential Anticholinesterase Activities

Development of a New Class of Monoamine Oxidase-B Inhibitors by Fine-Tuning the Halogens on the Acylhydrazones

3-Phenethyl-2-phenylquinazolin-4(3H)-one isolated from marine-derived Acremonium sp. CNQ-049 as a dual- functional inhibitor of monoamine oxidases-B and butyrylcholinesterase

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