The effect of brimonidine and proparacaine on metabolic enzymes: Glucose‐6‐phosphate dehydrogenase, 6‐phosphogluconate dehydrogenase, and glutathione reductase

Çalışkan, Büşra; Kesebir, Arzu Öztürk; Demir, Yeliz; Salman, İlknur Akyol

doi:10.1002/bab.2107

Cited by 18 publications

(15 citation statements)

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“…To investigate the in vitro inhibitory mechanisms of the novel synthesized N -substituted sulfonyl amides ( 6a–j ) incorporating 1,3,4-oxadiazol structural motif, kinetic studies were made with the variable compound and substrate concentrations, and IC 50 curves, Michaelis–Menten graphs [ 49 – 51 ], and Lineweaver–Burk curves [ 52 – 54 ] were generated as previously reported by Türkeş et al . [ 55 – 57 ].…”

Section: Methodsmentioning

confidence: 99%

Cytotoxic effect, enzyme inhibition, and in silico studies of some novel N-substituted sulfonyl amides incorporating 1,3,4-oxadiazol structural motif

et al. 2022

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The acetylcholinesterase and carbonic anhydrase inhibitors (AChEIs and h CAIs) remain key therapeutic agents for many bioactivities such as anti-Alzheimer and antiobesity antiepileptic, anticancer, antiinfective, antiglaucoma, and diuretic effects. Here, it has been attempted to discover novel multi-target AChEIs and h CAIs that are highly potent, orally bioavailable, may be brain penetrant, and have higher effectiveness at lower doses than tacrine and acetazolamide. After detailed investigations both in vitro and in silico, novel N -substituted sulfonyl amide derivatives ( 6a–j ) were determined to be highly potent inhibitors for AChE and h CAs ( K I s are in the range of 23.11–52.49 nM, 18.66–59.62 nM, and 9.33–120.80 nM for AChE, h CA I, and h CA II, respectively). Moreover, according to the cytotoxic effect studies, such as the ADME-Tox, cortex neuron cells, and neuroblastoma SH-SY5Y cell line, compounds 6a , 6d , and 6h , which are the most potent representative versus the target enzymes, were identified as orally bioavailable, highly selective, and brain preferentially distributed AChEIs and h CAIs. The docking studies revealed precise binding modes between 6a , 6d , and 6h and h CA II, h CA I, and AChE, respectively. The results presented here might provide a solid basis for further investigation into more potent AChEIs and h CAIs. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s11030-022-10422-8.

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Section: Methodsmentioning

confidence: 99%

Cytotoxic effect, enzyme inhibition, and in silico studies of some novel N-substituted sulfonyl amides incorporating 1,3,4-oxadiazol structural motif

et al. 2022

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“…To control enzyme purity, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE) was used 33‐35 . The activities of G6PD and 6PGD enzymes were based on converting enzymes NADP + to NADPH at 25°C and determining the absorbance of NADPH at 340 nm spectrophotometrically 36,37 . The IC 50 values, the inhibitory concentration that reduces the enzyme activity by 50%, were calculated from activity (%) vs compounds plots.…”

Section: Methodsmentioning

confidence: 99%

“…[33][34][35] The activities of G6PD and 6PGD enzymes were based on converting enzymes NADP + to NADPH at 25 C and determining the absorbance of NADPH at 340 nm spectrophotometrically. 36,37 The IC 50 values, the inhibitory concentration that reduces the enzyme activity by 50%, were calculated from activity (%) vs compounds plots. To obtain K I values and inhibition types, three different inhibitory concentrations were used.…”

Section: Enzyme Purification and Inhibition Studymentioning

confidence: 99%

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Screening of in vitro and in silico effect of Fluorophenylthiourea compounds on glucose 6‐phosphate dehydrogenase and 6‐phosphogluconate dehydrogenase enzymes

Yıldız

Demir

Küfrevioğlu

2022

J of Molecular Recognition

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Inhibition studies of enzymes in the pentose phosphate pathway (PPP) have recently emerged as a promising technique for pharmacological intervention in several illnesses. Glucose 6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) are the most important enzymes of the PPP. For this purpose, in the current study, we examined the effect of some fluorophenylthiourea on G6PD and 6PGD enzyme activity. These compounds exhibited moderate inhibitory activity against G6PD and 6PGD with K I values ranging from 21.60 ± 8.42 to 39.70 ± 11.26 μM, and 15.82 ± 1.54 to 29.97 ± 5.72 μM, respectively.2,6-difluorophenylthiourea displayed the most potent inhibitory effect for G6PD, and 2-fluorophenylthiourea demonstrated the most substantial inhibitory effect for 6PGD. Furthermore, the molecular docking analyses of the fluorophenylthioureas, competitive inhibitors, were performed to understand the binding interactions at the enzymes' binding site.6-phosphogluconate dehydrogenase, fluorophenylthiourea, glucose 6-phosphate dehydrogenase, molecular docking | INTRODUCTIONOne of the main intracellular reducing agents, nicotinamide adenine dinucleotide phosphate (NADPH), is mainly produced by the pentose phosphate pathway (PPP) and is crucial for the thioredoxin and glutathione systems. 1-4 PPP is the main pathway for glucose catabolism and the biosynthesis of aromatic amino acids, nucleic acids, glucose 6-phosphate dehydrogenase (G6PD), and 6-phosphogluconate dehydrogenase (6PGD) enzymes. These enzymes are the most important enzymes of the PPP play an essential role in the formation of NADPH. [5][6][7][8] On the other hand, an activated PPP affects tumor metabolism, such as angiogenesis, favoring tumor metastasis, promoting malignant transformation, protecting cells from apoptosis, and increasing tumor progression. [9][10][11][12] In recent years, overexpression of PPP enzymes in many types of cancer has been the focus of interest for researchers. The mechanism of PPP enzymes associated with cancer progression is still under investigation. The research found that 6PGD was regulated in many types of cancer, such as colon, leukemia, breast, ovarian, liver, and thyroid. [13][14][15] Thiourea structures have several biological activities, like anticancer and antibacterial activities, and especially on the central nervous system of rodents, they have a high impact. [16][17][18] The thiourea skeleton has an essential role in pharmaceutical chemistry. Studies have shown solid cytotoxic activity against cancer cells. [19][20][21] The desired inhibitory activity of these drugs against various inhibitors is crucial in the death of cancer cells. Recently, evaluation of novel derivatives of thiourea as anti-angiogenic and antitumor agents has been published. [22][23][24]

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“…All the docking simulations were performed through Glide extra precision (XP) mode 53 . Lastly, MM‐GBSA solvation in the VSGB energy model 54–56 and OPLS4 force field was utilized to compute the binding energies for the best poses of PON1 with these drugs from Glide XP docking simulations 57,58 …”

Section: Methodsmentioning

confidence: 99%

Ophthalmic drugs: in vitro paraoxonase 1 inhibition and molecular docking studies

Çalışkan¹,

Demir

Türkeş

2021

Biotech and App Biochem

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Glaucoma is a neuropathy disorder and is generally treated by drugs. Allergic conjunctivitis is a common ophthalmologic disease. Paraoxonase 1 (PON1) is an organophosphate hydrolyzer and antiatherogenic enzyme. PON1 is known for preventing atherosclerosis through lipid-modifying features, as well as which has decisive actions of antiapoptosis, anti-inflammatory, antithrombosis, and antiadhesion antioxidant activity properties. Thus, reducing the enzyme levels in hyperthyroidism, chronic renal failure, glaucoma, diabetes mellitus, and cardiovascular diseases is a significant risk. This study was tested some ophthalmic drugs used to treat the diseases, such as glaucoma and allergic conjunctivitis, mentioned above, travoprost, latanoprost, ketotifen, emedastine, and olopatadine, for their inhibition activities against PON1. These drugs displayed the potent inhibition effect with IC 50 values ranging between 14.95 ± 0.15 and 299.60 ± 4.07 μM and K I constants ranging from 9.71 ± 2.63 to 261.50 ± 59.98 μM. Besides, the molecular docking analyses of the competitive inhibitors, travoprost, emedastine, and olopatadine, were performed to understand the binding interactions on the enzyme's binding site. According to both in vitro and in silico analysis results, travoprost had the most potent effect on PON1 enzyme activity.

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The effect of brimonidine and proparacaine on metabolic enzymes: Glucose‐6‐phosphate dehydrogenase, 6‐phosphogluconate dehydrogenase, and glutathione reductase

Cited by 18 publications

References 83 publications

Cytotoxic effect, enzyme inhibition, and in silico studies of some novel N-substituted sulfonyl amides incorporating 1,3,4-oxadiazol structural motif

Cytotoxic effect, enzyme inhibition, and in silico studies of some novel N-substituted sulfonyl amides incorporating 1,3,4-oxadiazol structural motif

Screening of in vitro and in silico effect of Fluorophenylthiourea compounds on glucose 6‐phosphate dehydrogenase and 6‐phosphogluconate dehydrogenase enzymes

Ophthalmic drugs: in vitro paraoxonase 1 inhibition and molecular docking studies

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