4-Oxobenzo[d]1,2,3-triazin-pyridinium-phenylacetamide derivatives as new anti-Alzheimer agents: design, synthesis, in vitro evaluation, molecular modeling, and molecular dynamic study

Hosseini, Fahimeh Sadat; Mohammadi‐Khanaposhtani, Maryam; Azizian, Homa; Ramazani, Ali; Tehrani, Maliheh Barazandeh; Nadri, Hamid; Larijani, Bagher; Biglar, Mahmoud; Adibi, Hos­sein; Mahdavi, Mohammad

doi:10.1007/s11224-019-01472-0

Cited by 8 publications

(4 citation statements)

References 20 publications

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“…According to the previous synthesis methods and literature reports, we synthesized 30 compounds. [19][20][21][22][23] The synthesis route is shown in Scheme 1. Intermediate 3 was synthesized using 2-hydroxy-4methoxybenzaldehyde (2) and ethyl isocyanoacetate (1) as starting materials and copper iodide as a catalyst.…”

Section: Chemistrymentioning

confidence: 99%

Design, synthesis, and evaluation of dual‐target inhibitors for the treatment of Alzheimer's disease

Zhai,

Hao,

Wang

et al. 2024

Archiv der Pharmazie

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Aβ1−42 and acetylcholinesterase (AChE) are two key therapeutic targets for Alzheimer's disease (AD). The purpose of this study is to develop a dual‐target inhibitor that inhibits both of these targets by fusing the chemical structure of baicalein and donepezil. Among them, we modified the structure of baicalein to arylcoumarin, synthesized three kinds of structural compounds, and evaluated their biological activities. The results showed that compound 3b had the strongest inhibitory effect on AChE (IC50 = 0.05 ± 0.02 µM), which was better than those of donepezil and baicalein. In addition, compound 3b has a strong ability to inhibit the aggregation of Aβ1−42 and protect nerve cells, and it can also penetrate the blood–brain barrier well. Using a zebrafish behavioral analyzer test, it was found that compound 3b can alleviate the behavioral effects of AlCl3‐induced zebrafish larval movement retardation, which has a certain guiding significance for simulating the movement disorders of AD patients. In summary, compound 3b is expected to become a multifunctional agent for treating and alleviating the symptoms of AD patients.

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Section: Chemistrymentioning

confidence: 99%

Design, synthesis, and evaluation of dual‐target inhibitors for the treatment of Alzheimer's disease

Zhai,

Hao,

Wang

et al. 2024

Archiv der Pharmazie

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“…[ 15,16 ] For example, AChE inhibitors D and E have N ‐phenylacetamide derivatives in their structures. [ 17,18 ] The survey on ensaculin and structures of compounds A–E led us to design a novel series of 4‐phenylpiperazine‐carbodithioate‐ N ‐phenylacetamide derivatives 6a–n through molecular hybridization approach as cholinesterase inhibitors. These compounds were synthesized by simple and efficient reactions and evaluated against AChE and BChE.…”

Section: Introductionmentioning

confidence: 99%

“…[15,16] For example, AChE inhibitors D and E have N-phenylacetamide derivatives in their structures. [17,18] The survey on ensaculin and structures of compounds…”

mentioning

confidence: 99%

New 4‐phenylpiperazine‐carbodithioate‐N‐phenylacetamide hybrids: Synthesis, in vitro and in silico evaluations against cholinesterase and α‐glucosidase enzymes

Mohammadi‐Khanaposhtani

Nori

Valizadeh

et al. 2022

Archiv der Pharmazie

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A series of novel 4-phenylpiperazine-carbodithioate-N-phenylacetamide hybrids (6a-n) was designed, synthesized, and evaluated for their in vitro inhibitory activity against the metabolic enzymes, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glucosidase. The obtained results showed that most of the synthesized compounds exhibited high to good anti-AChE and anti-BChE activity in the range of nanomolar concentrations in comparison to tacrine as a positive control.Molecular modeling of the most potent compounds 6e and 6i demonstrated that these compounds interacted with important residues of the AChE and BChE active sites. Moreover, all the newly synthesized compounds 6a-n had significant K i values against α-glucosidase when compared with the positive control acarbose. Representatively, N-2-fluorophenylacetamide derivative 6l, with a K i value of 0.98 nM as the most potent compound, was 126 times more potent than acarbose with a K i value of 123.70 nM. This compound also fitted in the α-glucosidase active site and interacted with key residues. An in silico study of the druglikeness/absorption, distribution, metabolism, and excretion (ADME)/toxicity profile of the selected compounds 6e, 6i, and 6l predicts that these compounds are drug-like and have the appropriate properties in terms of ADME and toxicity.

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“…Heterocyclic compound having a significant and unique position in medicinal chemistry. [ 1 ] Synthesis of such heterocyclic compound have acquired high priority in the pharmaceutical field [ 2–4 ] because they shows a wide range of interesting biological activities, such as antimicrobial, [ 5 ] anti‐inflammatory, [ 6 ] antioxidant, [ 7 ] antiviral, [ 8 ] antibacterial, [ 9 ] anticancer, [ 10 ] anticonvulsant, [ 11 ] cardiovascular, [ 12 ] antihypertensive, [ 13 ] antipyretic, [ 14 ] antibiotic, [ 15 ] anti‐hyperglycemic activity. [ 16 ] Among these heterocyclic compounds, the five membered heterocyclic aromatic ring compound having lots of applications in pharmaceutical field.…”

Section: Introductionmentioning

confidence: 99%

Sodium toluene‐4‐sulfonate as a reusable and ecofriendly catalyst for greener synthesis of 5‐aminopyrazole‐4‐carbonitrile in aqueous medium

Sapkal¹,

Kamble²

2020

Journal of Heterocyclic Chem

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In these environmentally conscious days there is need to use eco-friendly greener technologies, such as solvent free, microwave, ultrasound and use of room temperature. Here report an efficient and green protocol for the synthesis of 5-aminopyrazole-4-carbonitrile from three component condensation of phenyl hydrazine, aldehyde, and malononitrile using NaPTS as catalyst in aqueous medium. Use of water has emerged as a versatile solvent for organic reaction; it is readily available, inexpensive, environmentally benign, neutral and natural solvent. Multicomponent reactions in water are of outstanding value in organic synthesis and green chemistry. The significant features of this article are short reaction time, provide excellent yield, removal of toxic solvent and use of water as green solvent.

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4-Oxobenzo[d]1,2,3-triazin-pyridinium-phenylacetamide derivatives as new anti-Alzheimer agents: design, synthesis, in vitro evaluation, molecular modeling, and molecular dynamic study

Cited by 8 publications

References 20 publications

Design, synthesis, and evaluation of dual‐target inhibitors for the treatment of Alzheimer's disease

Design, synthesis, and evaluation of dual‐target inhibitors for the treatment of Alzheimer's disease

New 4‐phenylpiperazine‐carbodithioate‐N‐phenylacetamide hybrids: Synthesis, in vitro and in silico evaluations against cholinesterase and α‐glucosidase enzymes

Sodium toluene‐4‐sulfonate as a reusable and ecofriendly catalyst for greener synthesis of 5‐aminopyrazole‐4‐carbonitrile in aqueous medium

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