Enzyme inhibition, molecular docking, and density functional theory studies of new thiosemicarbazones incorporating the 4‐hydroxy‐3,5‐dimethoxy benzaldehyde motif

Demir, Yeliz; Türkeş, Cüneyt; Çavuş, M. Serdar; Erdoğan, Musa; Muğlu, Halit; Yakan, Hasan; Beydemır, Şükrü

doi:10.1002/ardp.202200554

Cited by 24 publications

(21 citation statements)

References 90 publications

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“…The scoring function was employed to execute extra precision glide calculations (XP) with greater accuracy. [65][66][67] The VSGB energy model and the OPLS4 force field were employed to compute MM-GBSA binding energies, which predicted relative binding affinities for a series of methyl benzoate derivatives (1 a-16 a). [68][69]…”

Section: Docking Studymentioning

confidence: 99%

Screening of in Vitro Inhibition of Lactoperoxidase Enzyme by Methyl Benzoate Derivatives with Molecular Docking Studies

Abul

Gerni

Korkmaz

et al. 2023

Chemistry & Biodiversity

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Lactoperoxidase enzyme (LPO) is secreted from salivary, mammary, and other mucosal glands including the bronchi, lungs, and nose, which had functions as a natural and the first line of defense towards viruses and bacteria. In this study, methyl benzoates were examined in LPO enzyme activity. Methyl benzoates are used as precursors in the synthesis of aminobenzohydrazides used as LPO inhibitors. For this purpose, LPO was purified in a single step using sepharose‐4B‐l‐tyrosine‐sulfanilamide affinity gel chromatography with a yield of 9.91 % from cow milk. Also, some inhibition parameters including the half maximal inhibitory concentration (IC50) value and an inhibition constant (Ki) values of methyl benzoates were determined. These compounds inhibited LPO with Ki values ranging from 0.033±0.004 to 1540.011±460.020 μM. Compound 1 a (methyl 2‐amino‐3‐bromobenzoate) showed the best inhibition (Ki=0.033±0.004 μM). The most potent inhibitor (1 a) showed with a docking score of −3.36 kcal/mol and an MM‐GBSA value of −25.05 kcal/mol, of these methyl benzoate derivatives (1 a–16 a) series are established H‐bond within the binding cavity with residues Asp108 (distance of 1.79 Å), Ala114 (distance of 2.64 Å), and His351 (distance of 2.12 Å).

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Section: Docking Studymentioning

confidence: 99%

Screening of in Vitro Inhibition of Lactoperoxidase Enzyme by Methyl Benzoate Derivatives with Molecular Docking Studies

Abul

Gerni

Korkmaz

et al. 2023

Chemistry & Biodiversity

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“…LigPrep [44] and the OPLS4 [45] force eld were used to prepare and minimize the 3D structures of the novel 1,3-diaryltriazene-substituted sulfaguanidine derivatives (SG1-13). AZM was used as the centroid to create a grid [46], and the glide extra precision (XP) docking procedure [47][48][49] was used as in our previous studies [50,51]. Flexible ligand sampling was used, and the docking score included Epik state penalties [52][53][54].…”

Section: Computational Studiesmentioning

confidence: 99%

Novel 1,3-diaryltriazene-substituted sulfaguanidine derivatives as selective carbonic anhydrase inhibitors: Synthesis, characterization, inhibition effects, and molecular docking studies

Akocak

Lolak

Duran

et al. 2023

Preprint

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Sulfonamide compounds known as human carbonic anhydrase (hCA) inhibitors are used in the treatment of many diseases such as epilepsy, antibacterial glaucoma, various diseases. 1,3-diaryl-substituted triazenes and sulfaguanidine are used for therapeutic purposes in many drug structures. Based on these two groups, the synthesis of new compounds is important. In the present study, the novel 1,3-diaryltriazene-substituted sulfaguanidine derivatives (SG1-13) were synthesized and fully characterized by spectroscopic and analytic methods. Inhibitory effect of the these compounds on the hCA I and hCA II was screened as in vitro. All the series of synthesized compounds have been identified as potential hCA isoenzymes inhibitory with KI values in the range of 6.44 ± 0.74–86.85 ± 7.01 nM for hCA I and with KI values in the range of 8.16 ± 0.40-77.29 ± 9.56 nM for hCA II. Moreover, the new series of compounds showed a more effective inhibition effect than the acetazolamide used as a reference. The possible binding positions of the compounds with a binding affinity to the hCA I and hCA II was demonstrated by in silico studies. In conclusion, compounds with varying degrees of affinity for hCA isoenzymes have been designed and as selective hCA inhibitors, the compounds may be potential alternative agents that can be used to treat or prevent diseases associated with glaucoma and hCA inhibition.

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“…[67] Additionally, the crystal structures of two enzymes, AChE [53] and BChE [54] (PDB codes of 7XN1 and 4BDS, respectively), were obtained from the Protein Data Bank [68] and optimized using the Protein Preparation Wizard tool. [69] This was done using the force field OPLS4, [70] with default parameters set at pH 7.4 � 0.5. [71] The receptor binding sites were also identified using SiteMap software [72] based on the optimal score for the target Puerarin.…”

Section: In Silico Studymentioning

confidence: 99%

Determination of the Antioxidant Capacity of Puerarin and Its Effect on Cholinesterases by in vitro and in silico Methods

İnan Ergün,

Topal

2023

ChemistrySelect

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Puerarin, which was used as a natural isoflavone in this study, was obtained from the Kudzu plant. The inhibitory effect of puerarin on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes was investigated. The IC50 values of AChE (177.73 nM) and BChE (315.07 nM) were determined. The binding mechanism of puerarin, which has a high inhibitory effect on the active site of the enzyme, was demonstrated by the molecular docking method. The antioxidant activity was evaluated for the same molecule. For this purpose, Fe3+‐Fe2+ reducing capacity, ABTS radical scavenging activity, CUPRAC method, DPPH⋅ scavenging activity and DMPD radical scavenging method were used. The percentage (%) inhibition amount of puerarin molecule was calculated as 99.33 % for ABTS radical scavenging activity, which is the more preferred method for natural products. The absorbtion value of iron reduction of Puerarin was 0.122±0.010, and the value of copper reduction was 0.633±0.026. Our research efforts include uncovering the potent antioxidant potential of puerarin and, simultaneously, a comparative study of tacrine, primarily emphasizing its inhibitory effects against AChE and BChE enzymes. The puerarin is expected to be a guide for drug discovery against many problems, especially oxidative cell damage in Alzheimer's disease, mitochondrial dysfunction (MD), cancer, and cardiovascular diseases.

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Enzyme inhibition, molecular docking, and density functional theory studies of new thiosemicarbazones incorporating the 4‐hydroxy‐3,5‐dimethoxy benzaldehyde motif

Cited by 24 publications

References 90 publications

Screening of in Vitro Inhibition of Lactoperoxidase Enzyme by Methyl Benzoate Derivatives with Molecular Docking Studies

Screening of in Vitro Inhibition of Lactoperoxidase Enzyme by Methyl Benzoate Derivatives with Molecular Docking Studies

Novel 1,3-diaryltriazene-substituted sulfaguanidine derivatives as selective carbonic anhydrase inhibitors: Synthesis, characterization, inhibition effects, and molecular docking studies

Determination of the Antioxidant Capacity of Puerarin and Its Effect on Cholinesterases by in vitro and in silico Methods

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