Hydrazones of 4-(Trifluoromethyl)benzohydrazide as New Inhibitors of Acetyl- and Butyrylcholinesterase

Krátký, Martin; Svrčková, Katarína; Vu, Quynh Anh; Štěpánková, Šárka; Vinšová, Jarmila

doi:10.3390/molecules26040989

Cited by 17 publications

(10 citation statements)

References 31 publications

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“…Hydrazone nucleus, as a fusion of amide and imine subunits, possess hydrogen-bond donor and acceptor sites for interaction with amino acid residues [ 18 ]. Thus, compounds with hydrazone cores express inhibitory effects against numerous enzymes, such as cyclooxygenase (COX-1 and COX-2) [ 20 , 34 ], acetyl- and butyrylcholinesterase (AChE and BuChE) [ 35 ], monoamine oxidase A (MAO A) [ 36 ], as well as G-Protein-Coupled Receptor Kinase 2 (GRK2) involved in heart failure [ 37 ]. Particularly, the N -acylhydrazone group ( N AH ) is declared as a unique and versatile structural motif, suitable for synthetic transformations and the development of potential therapeutically useful compounds [ 38 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of antioxidant and cytotoxic properties of phenolic N -acylhydrazones: structure–activity relationship

et al. 2022

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Cancer is still a relentless public health issue. Particularly, colorectal cancer is the third most prevalent cancer in men and the second in women. Moreover, cancer development and growth are associated with various cell disorders, such as oxidative stress and inflammation. The quest for efficient therapeutics is a challenging task, especially when it comes to achieving both cytotoxicity and selectivity. Herein, five series of phenolic N -acylhydrazones were synthesized and evaluated for their antioxidant potency, as well as their influence on HCT-116 and MRC-5 cells viability. Among 40 examined analogues, 20 of them expressed antioxidant activity against the DPPH radical. Furthermore, density functional theory was employed to estimate the antioxidant potency of the selected analogues from the thermodynamical aspect, as well as the preferable free-radical scavenging pathway. Cytotoxicity assay exposed enhanced selectivity of a number of analogues toward cancer cells. The structure–activity analysis revealed the impact of the type and position of the functional groups on both cell viability and selectivity toward cancer cells.

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Section: Introductionmentioning

confidence: 99%

Evaluation of antioxidant and cytotoxic properties of phenolic N -acylhydrazones: structure–activity relationship

et al. 2022

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“…Interestingly, the compound ( 16 ) (IC 50 =1.50±0.10 μM against AChE) has a better selectivity index (2.60) for AChE over BuChE. The selectivity toward AChE is interesting for these two compounds when comparing with the selectivity of Donepezil (selectivity index=2.083) [36–38] …”

Section: Resultsmentioning

confidence: 99%

Synthesis and Molecular Docking of New Bis‐Thiazolidinone‐Based Chalcone Analogs as Effective Inhibitors of Acetylcholinesterase and Butyrylcholinesterase

Hussain

Rehman

Taha

et al. 2022

Chemistry & Biodiversity

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This work reports the convenient strategy for the synthesis of bis-thiazolidinone based chalcone analogs (1 -20) from readily available thiosemicarbazide hydrochloride, ammonium thiocyanate and benzaldehyde. All the newly afforded bis-thiazolidinone based chalcone analogs (1 -20) were screened in vitro for their acetylcholinesterase and butyrylcholinesterase inhibition profile. It was noteworthy, that all the synthetic analogs (except analogs 10, 12 and 14, which are found to be inactive) showed moderate to good inhibitory potentials on screening against acetylcholinesterase having range of inhibitory with IC 50 values from 0.070 � 0.050 to 7.60 � 0.10 μM, and similarly for butyrylcholinesterase with range IC 50 values from 0.10 � 0.050 μM to 10.70 � 0.20 μM, respectively as compared to standard Donepezil inhibitor (IC 50 = 2.16 � 0.12 μM), (IC 50 = 4.5 � 0.11 μM).Among the series, the analogs with hydroxy group showed superior inhibitory potentials against acetylcholinesterase and butyrylcholinesterase enzymes. Therefore, analog 20 (IC 50 = 0.070 � 0.050 μM), (IC 50 = 0.10 � 0.050 μM) bearing trihydroxy substitutions on ortho-, meta-and para-position of both rings A and B was found to be the most active inhibitor of acetylcholinesterase and butyrylcholinesterase enzymes among the current synthesized series (1 -23). Analog 19 (IC 50 = 0.15 � 0.050 μM), (IC 50 = 0.20 � 0.050 μM) bearing dihydroxy substitutions on ortho-and meta-position of both ring A and ring B was identified as the second most potent inhibitor against both these enzymes. Interestingly, the compound (16) (IC 50 = 1.50 � 0.10 μM against AChE) has a better selectivity index (2.60) than standard Donepezil drug (2.083) for AChE over BuChE. The different types of spectroscopic techniques such as HR-EI-MS, 1 H-and 13 C-NMR were used to confirm the structure of all the newly synthetics analogs. To find structure-activity relationship, molecular docking studies were carried out to understand the binding mode of active inhibitors with active site of enzymes and results supported the experimental data.

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“…To date, many studies have been carried out on aryl OH-substituted hydrazidehydrazones (see Figure 1), covering several biological aspects, such as antimicrobial [31][32][33][34][35], antiviral [33,[36][37][38][39], anticancer [40][41][42][43], antiradical [31,44], enzyme inhibitors [40, [44][45][46][47][48][49], cytotoxicity [36,50], and photophysical activity [51,52]. Recently, Mali et al [33] and Popiołek [32] published exhaustive, comprehensive reviews on the biological activity, including antimicrobial activity, of hydrazides and their derivatives.…”

Section: Introductionmentioning

confidence: 99%

4-Hydroxybenzoic Acid-Based Hydrazide–Hydrazones as Potent Growth Inhibition Agents of Laccase-Producing Phytopathogenic Fungi That Are Useful in the Protection of Oilseed Crops

Maniak,

Matyja,

Pląskowska

et al. 2024

Molecules

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The research on new compounds against plant pathogens is still socially and economically important. It results from the increasing resistance of pests to plant protection products and the need to maintain high yields of crops, particularly oilseed crops used to manufacture edible and industrial oils and biofuels. We tested thirty-five semi-synthetic hydrazide–hydrazones with aromatic fragments of natural origin against phytopathogenic laccase-producing fungi such as Botrytis cinerea, Sclerotinia sclerotiorum, and Cerrena unicolor. Among the investigated molecules previously identified as potent laccase inhibitors were also strong antifungal agents against the fungal species tested. The highest antifungal activity showed derivatives of 4-hydroxybenzoic acid and salicylic aldehydes with 3-tert-butyl, phenyl, or isopropyl substituents. S. sclerotiorum appeared to be the most susceptible to the tested compounds, with the lowest IC50 values between 0.5 and 1.8 µg/mL. We applied two variants of phytotoxicity tests for representative crop seeds and selected hydrazide–hydrazones. Most tested molecules show no or low phytotoxic effect for flax and sunflower seeds. Moreover, a positive impact on seed germination infected with fungi was observed. With the potential for application, the cytotoxicity of the hydrazide–hydrazones of choice toward MCF-10A and BALB/3T3 cell lines was lower than that of the azoxystrobin fungicide tested.

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Hydrazones of 4-(Trifluoromethyl)benzohydrazide as New Inhibitors of Acetyl- and Butyrylcholinesterase

Cited by 17 publications

References 31 publications

Evaluation of antioxidant and cytotoxic properties of phenolic N -acylhydrazones: structure–activity relationship

Evaluation of antioxidant and cytotoxic properties of phenolic N -acylhydrazones: structure–activity relationship

Synthesis and Molecular Docking of New Bis‐Thiazolidinone‐Based Chalcone Analogs as Effective Inhibitors of Acetylcholinesterase and Butyrylcholinesterase

4-Hydroxybenzoic Acid-Based Hydrazide–Hydrazones as Potent Growth Inhibition Agents of Laccase-Producing Phytopathogenic Fungi That Are Useful in the Protection of Oilseed Crops

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