Identification of Lignan Compounds as New 6-Phosphogluconate Dehydrogenase Inhibitors for Lung Cancer

Khan, Gul Bushra; Qasim, Muhammad; Rasul, Azhar; Ashfaq, Usman Ali; Alnuqaydan, Abdullah M

doi:10.3390/metabo13010034

Cited by 4 publications

(1 citation statement)

References 62 publications

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“…Their findings revealed that among these compounds, 2‐fluorophenylthiourea exhibited the most pronounced inhibitory effect on this enzyme. In a study by Khan et al 66 an exhaustive screening of 17,000 natural compounds was carried out to assess their interaction with the 3‐PG binding site of 6PGD, utilizing the molecular operating environment. This screening revealed 115 inhibitors that displayed heightened selectivity and binding affinity.…”

Section: Resultsmentioning

confidence: 99%

Some pyrroles as inhibitors of the pentose phosphate pathways enzymes: An in vitro and molecular docking study

Özaslan

2024

J of Molecular Recognition

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Glucose‐6‐phosphate dehydrogenase (G6PD) and 6‐phosphogluconate dehydrogenase (6PGD) are pentose phosphate pathway enzymes. Compounds with a heterocyclic pyrrole ring system containing this atom can be derivatized with various functional groups into highly effective bioactive agents. In this study, pyrrole derivatives on these enzyme's activity were investigated. The IC50 values of different concentrations of pyrrole derivatives for G6PD were found in the range of 0.022–0.221 mM Ki values 0.021 ± 0.003–0.177 ± 0.021 and for 6PGD IC50 values 0.020–0.147, mM Ki values 0.013 ± 0.002–0.113 ± 0.030 mM. The 2‐acetyl‐1‐methylpyrrole (1g) showed the best inhibition value for G6PD and 6PGD enzymes. In addition, in silico molecular docking experiments were performed to elucidate how these pyrrole derivatives (1a–g) interact with the binding sites of the target enzymes. The study's findings on pyrrole derivatives could be used to create innovative therapeutics that could be a treatment for many diseases, especially cancer manifestations.

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Section: Resultsmentioning

confidence: 99%

Some pyrroles as inhibitors of the pentose phosphate pathways enzymes: An in vitro and molecular docking study

Özaslan

2024

J of Molecular Recognition

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The enzymes of the oxidative phase of the pentose phosphate pathway as targets of reactive species: consequences for NADPH production

Fuentes-Lemus,

Reyes,

Figueroa

et al. 2023

Biochemical Society Transactions

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The pentose phosphate pathway (PPP) is a key metabolic pathway. The oxidative phase of this process involves three reactions catalyzed by glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconolactonase (6PGL) and 6-phosphogluconate dehydrogenase (6PGDH) enzymes. The first and third steps (catalyzed by G6PDH and 6PGDH, respectively) are responsible for generating reduced nicotinamide adenine dinucleotide phosphate (NAPDH), a key cofactor for maintaining the reducing power of cells and detoxification of both endogenous and exogenous oxidants and electrophiles. Despite the importance of these enzymes, little attention has been paid to the fact that these proteins are targets of oxidants. In response to oxidative stimuli metabolic pathways are modulated, with the PPP often up-regulated in order to enhance or maintain the reductive capacity of cells. Under such circumstances, oxidation and inactivation of the PPP enzymes could be detrimental. Damage to the PPP enzymes may result in a downward spiral, as depending on the extent and sites of modification, these alterations may result in a loss of enzymatic activity and therefore increased oxidative damage due to NADPH depletion. In recent years, it has become evident that the three enzymes of the oxidative phase of the PPP have different susceptibilities to inactivation on exposure to different oxidants. In this review, we discuss existing knowledge on the role that these enzymes play in the metabolism of cells, and their susceptibility to oxidation and inactivation with special emphasis on NADPH production. Perspectives on achieving a better understanding of the molecular basis of the oxidation these enzymes within cellular environments are given.

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Neuroprotective Efficacy of Phytoconstituents of Methanolic Shoots Extract of Calligonum polygonoides L. in Hypercholesterolemia-associated Neurodegenerations

Sakarwal,

Sen,

Ram

et al. 2025

EMIDDT

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Background: Small molecule phytocompounds can potentially ameliorate degenerative changes in cerebral tissues. Thus, the current study aimed to evaluate the neuroprotective efficacy of phytocompounds of methanolic shoots extract of Calligonum polygonoides L. (MSECP) in hypercholesterolemia-associated neurodegenerations. background: Hypercholesterolemia-associated neurodegenerations are leading complications in cardiovascular diseases (CVD). Methods: Phytochemical screening of the extract was made by LCMS/MS and validated by a repository of the chemical library. The hypercholesterolemia was induced through the intraperitoneal administration of poloxamer-407 with a high-fat diet. The in-silico assessments were accomplished by following the molecular docking, ADME and molecular dynamics. MMPBSA and PCA (Principal Component Analysis) analyzed the molecular dynamics simulations. Consequently, in-vivo studies were examined by lipid metabolism, free radical scavenging capabilities and histopathology of brain tissues (cortex and hippocampus). objective: To examine target enzymes (AChE and BuChE) inhibition and free radicals scavenging capabilities by leading compound. Results: 22 leading phytocompounds were exhibited in the test extract, as revealed by LCMS/ MS scrutiny. Molecular docking evaluated significant interactions of apigenin triacetate with target proteins (HMGCR (HMG-CoA reductase), (AChE-Acetylcholinesterase) and (BuChE- Butyrylcholinesterase). Molecular dynamics examined the interactions through assessments of the radius of gyration, RSMD, RSMF and SASA at 100 ns, which were further analyzed by MMPBSA (Molecular Mechanics Poisson-Boltzmann) and PCA (Principal Component Analysis). Accordingly, the treatment of test extract caused significant alterations in lipid profile, dyslipidemia indices, antioxidant levels and histopathology of brain tissues. Conclusion: It can be concluded that apigenin triacetate is a potent phytoconstituent of MSEPC and can interact with HMGCR, AChE, and BuChE, which resulted in improved hypercholesterolemia along with neuroprotective ameliorations in the cortex and hippocampus.

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Identification of Lignan Compounds as New 6-Phosphogluconate Dehydrogenase Inhibitors for Lung Cancer

Cited by 4 publications

References 62 publications

Some pyrroles as inhibitors of the pentose phosphate pathways enzymes: An in vitro and molecular docking study

Some pyrroles as inhibitors of the pentose phosphate pathways enzymes: An in vitro and molecular docking study

The enzymes of the oxidative phase of the pentose phosphate pathway as targets of reactive species: consequences for NADPH production

Neuroprotective Efficacy of Phytoconstituents of Methanolic Shoots Extract of Calligonum polygonoides L. in Hypercholesterolemia-associated Neurodegenerations

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