Synthesis of novel thiazolyl hydrazone derivatives as potent dual monoamine oxidase-aromatase inhibitors

Evren, Asaf Evrim; Nuha, Demokrat; Dawbaa, Sam; Sağlık, Begüm Nurpelin; Yurttaş, Leyla

doi:10.1016/j.ejmech.2021.114097

Cited by 30 publications

(19 citation statements)

References 43 publications

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“…According to the literature, all the mentioned amino acids were described as significant residues, but amino acids Tyr398 and Tyr435 were more attractive than the others because of their role in the enzyme mechanism. ,, Although there were a few differences between the interactions of compounds D29 and D37 , the experimental studies for both compounds were supported by molecular docking and molecular dynamic simulations and explained how the compounds bonded to or stabilized the enzyme active pocket. Due to their interaction with the FAD protein and closing the cavity of the substrate binding region, it was found that their main action mechanism was mainly related to the above explanation, but their distinct activity was related to which amino acids they bonded to.…”

Section: Resultsmentioning

confidence: 99%

“…All MDS were carried out for 100 ns to analyze the stability of the identified hits from the in vitro with docking results. System setup preparation, MDS, and interaction analysis calculations were carried out according to the same procedure from previous studies. , …”

Section: Methodsmentioning

confidence: 99%

“…The fluorometric approach, which was outlined in our team’s previously reported studies, was used to evaluate the synthesized compounds’ inhibitory effects against MAO-A and MAO-B. − The enzymes employed in the experiment were recombinant human MAO-A and MAO-B enzymes.…”

Section: Methodsmentioning

confidence: 99%

“…System setup preparation, MDS, and interaction analysis calculations were carried out according to the same procedure from previous studies. 24 , 40 …”

Section: Methodsmentioning

confidence: 99%

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Design, Synthesis, and In Vitro and In Silico Approaches of Novel Indanone Derivatives as Multifunctional Anti-Alzheimer Agents

et al. 2022

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Alzheimer’s disease (AD) is a neurological, progressive illness that typically affects the elderly and is clinically distinguished by memory and cognitive decline. Due to a number of factors, including the absence of a radical treatment, an increase in the patient population over time, the high cost of care and treatment, and a significant decline in patients’ quality of life, the importance of this disease has increased. These factors have all prompted increased interest among researchers in this field. The chemical structure of the donepezil molecule, the most popular and effective treatment response for AD, served as the basis for the design and synthesis of 42 novel indan-1-one derivatives in this study. Using IR, 1H, and 13C NMR as well as mass spectroscopic techniques, the compounds’ structures were identified. Research on the compounds’ antioxidant activities, cholinesterase (ChE) enzyme inhibition, monoamine oxidase (MAO) A and B inhibitory activities, β-amyloid plaque inhibition, and cytotoxicity impact was carried out. Inhibition of β-amyloid plaque aggregation; effective inhibition of AChE, BChE, and MAO-B enzymes; and significant antioxidant activity were all demonstrated by compounds D28–D30 and D37–D39. Because of their various actions, it was hypothesized that the related compounds may be useful in treating AD symptoms as well as providing palliative care.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…System setup preparation, MDS, and interaction analysis calculations were carried out according to the same procedure from previous studies. 24 , 40 …”

Section: Methodsmentioning

confidence: 99%

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Design, Synthesis, and In Vitro and In Silico Approaches of Novel Indanone Derivatives as Multifunctional Anti-Alzheimer Agents

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“…Because the current study is primarily concerned with evaluating activity, the active substances may be considered for in vivo pharmacokinetic investigations in the future. [60] As a result, the Swiss-ADME web-based application was used to determine the medicinal chemistry and pharmacokinetic profiles of the 2a-2j…”

Section: 3 | Prediction Of Physicochemical and Pharmacokinetic Proper...mentioning

confidence: 99%

Synthesis, density functional theory calculation, molecular docking studies, and evaluation of novel 5‐nitrothiophene derivatives for anticancer activity

Nuha

Evren

Çiyanci

et al. 2022

Archiv der Pharmazie

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Within the scope of this study, new 2-{2-[(5-nitrothiophen-2-yl)methylene] hydrazinyl}thiazole derivatives (2a-j) were synthesized and investigated for their potential anticancer and enzyme inhibition activities. Spectroscopic techniques were used to determine the structures of substances. The anticancer activities of compounds were detected in A549 human lung carcinoma and L929 murine fibroblast cell lines, determining cytotoxicity, apoptosis, mitochondrial membrane integrity, and caspase-3 activation. Compounds 2b bearing 4-nitrophenyl, 2c bearing phenyl, and 2d bearing 4-cyanophenyl moieties were specified with high anticancer activity, acting through an apoptotic pathway with an apoptosis ratio of 9.61%-15.59%. Mitochondrial membrane depolarization was determined to be 25.53% and 22.33% for compounds 2b and 2c, respectively. Furthermore, compound 2c exhibited excellent caspase-3 activation. A molecular docking study was realized with compound 2c on the caspase-3 enzyme. Furthermore, the electronic characteristics of the active compounds were investigated using density functional theory (DFT) at the B3LYP/6-31G (d, p) level. The frontier molecular orbital energy and atomic net charges were examined.

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Design, synthesis, biological evaluation, and molecular modeling simulations of new phthalazine‐1,4‐dione derivatives as anti‐Alzheimer's agents

Nuha,

Evren,

Özkan

et al. 2024

Archiv der Pharmazie

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The development of targeted phthalazine‐1,4‐dione acetylcholinesterase (AChE) inhibitors for treating Alzheimer's disease involved the synthesis of 32 compounds via a multistage process. Various analytical techniques confirmed the compounds' identities. Thirteen compounds were found to inhibit AChE by more than 50% without affecting butyrylcholinesterase (BChE). Among these, three compounds, 8m, 8n, and 8p, exhibited extraordinary activity similar to donepezil, a reference AChE inhibitor. During enzyme kinetic studies, compound 8n, displaying the highest AChE inhibitory activity, underwent evaluation at three concentrations (2 × IC50, IC50, and IC50/2). Lineweaver–Burk plots indicated mixed inhibition activity for compound 8n against AChE, suggesting a combination of competitive and noncompetitive characteristics. Additionally, effective derivatives 8m, 8n, and 8p exhibited high blood–brain barrier (BBB) permeability in in vitro parallel artificial membrane permeability assay tests. Molecular docking studies revealed that these compounds bind to the enzyme's active site residues in a position similar to donepezil. Molecular dynamic simulations confirmed the stability of the protein–ligand system, and the chemical reactivity characteristics of the compounds were investigated using density functional theory. The compounds' wide energy gaps suggest stability and therapeutic potential. This research represents a significant step toward finding a potential cure for Alzheimer's disease. However, further research and testing are required to determine the compounds' safety and efficacy. The unique structure of phthalazine derivatives makes them suitable for various biological activities, and these compounds show promise for developing effective drugs for treating Alzheimer's disease. Overall, the development of these targeted compounds is a crucial advancement in the search for an effective treatment for Alzheimer's disease.

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Synthesis of novel thiazolyl hydrazone derivatives as potent dual monoamine oxidase-aromatase inhibitors

Cited by 30 publications

References 43 publications

Design, Synthesis, and In Vitro and In Silico Approaches of Novel Indanone Derivatives as Multifunctional Anti-Alzheimer Agents

Design, Synthesis, and In Vitro and In Silico Approaches of Novel Indanone Derivatives as Multifunctional Anti-Alzheimer Agents

Synthesis, density functional theory calculation, molecular docking studies, and evaluation of novel 5‐nitrothiophene derivatives for anticancer activity

Design, synthesis, biological evaluation, and molecular modeling simulations of new phthalazine‐1,4‐dione derivatives as anti‐Alzheimer's agents

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