Association of human serum paraoxonase‐1 with some respiratory drugs

Gökçe, Başak; Sarıoğlu, Nurhan; Gençer, Nahit; Arslan, Oktay

doi:10.1002/jbt.22407

Cited by 7 publications

(6 citation statements)

References 30 publications

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“…Both complex 1 and 2 inhibited PON1 (associated with HDL) with Ki of 0.37 µM and 0.27 µM, respectively, as non-competitive inhibitors (Figure 4). These results demonstrated that complex 1 and have a much stronger PON1 inhibitory activity than the reported PON1 inhibitors (Ki or IC50 values ranging between 35 µM and 550 µM) in the literature [37][38][39]. Besides, the changing metals and their atomic diameters have not shown a significant effect on PON1 inhibition.…”

Section: Resultsmentioning

confidence: 50%

Evaluation of carbonic anhydrase and paraoxonase inhibition activities and molecular docking studies of highly water-soluble sulfonated phthalocyanines

et al. 2020

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The investigation of carbonic anhydrase and paraoxonase enzyme inhibition properties of water-soluble zinc and gallium phthalocyanine complexes (1 and 2) are reported for the first time. The binding of p-sulfonylphenoxy moieties to the phthalocyanine structure favours excellent solubilities in water, as well as providing inhibition effect on carbonic anhydrase (CA) I and II isoenzymes and paraoxonase (PON1) enzyme. According to biological activity results, both complexes inhibited hCA I, hCA II and PON1. Whereas 1 and 2 showed moderate hCA I and hCA II (off-target cytosolic isoforms) inhibitory activity (Ki values of 26.09 µM and 43.11 µM for hCA I and 30.95 µM and 33.19 µM for hCA II, respectively), they exhibited strong PON1 (associated with high-density lipoprotein (HDL)) inhibitory activity (Ki values of 0.37 µM and 0.27 µM, respectively). The inhibition kinetics was analyzed by Lineweaver-Burk double reciprocal plots. It revealed that 1 and 2 were non-competitive inhibitors against PON1, hCA I and hCA II. These complexes can be advantageous than other synthetic CA and PON inhibitors due to their water solubility. Docking studies were carried out to examine the interactions between hCA I, hCA II and PON1 inhibitors and metal complexes at molecular level and to predict binding energies.

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Section: Resultsmentioning

confidence: 50%

Evaluation of carbonic anhydrase and paraoxonase inhibition activities and molecular docking studies of highly water-soluble sulfonated phthalocyanines

et al. 2020

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“…LDL oxidation is maintained by PON1 activity during the initial stage of atherosclerosis 5–8 . In recent years, researchers have focused on the interaction of PON1 enzyme with different drugs and compounds to investigate the effects of this multifunctional enzyme, which is associated with many metabolic diseases, and attracts attention with its toxicological biomarker feature 36–42 …”

Section: Resultsmentioning

confidence: 99%

“…purified the PON1 enzyme and found that the molecular weight of the enzyme was 43 kDa and the isoelectric point of the enzyme was 5.1 10 . In the last decades, there has been an increasing number of studies on the purification of PON1 enzyme from different sources with various methods including sephadex, agarose, and sepharose 36,40,43 . More recently, attention has been focused on the provision of purification of PON1 enzyme with hydrophobic interaction chromatography due to its hydrophobic character 18,43–45 .…”

Section: Resultsmentioning

confidence: 99%

Evaluation of in vitro effect, molecular docking, and molecular dynamics simulations of some dihydropyridine‐class calcium channel blockers on human serum paraoxonase 1 (hPON1) enzyme activity

Gökçe

Muhammed

2023

Biotech and App Biochem

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Paraoxonase 1 (PON1) was purified 148.80‐fold in 37.92% yield by hydrophobic interaction chromatography technique. The purity of PON1 was checked by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE) with a single band of 43 kDa. The in vitro effects of nine different calcium channel blockers on PON1 activity were evaluated. All drugs strongly decreased PON1 activity, and IC50 levels were between 13.987 ± 0.59 and 238.104 ± 2.14 μM, Ki values between 8.58 ± 0.36 and 111 ± 1.27 μM. The drugs with the strongest inhibitory effect were nisoldipine with 13.987 ± 0.59 μM and nicardipine with 20.158 ± 0.43 μM. The mechanism of action for the inhibition of the enzyme by nisoldipine and nicardipine was investigated through molecular docking. The stability of enzyme–ligand complexes obtained from the docking was explored through molecular dynamics simulation. The binding affinity of the ligands toward the enzyme was also investigated through MMPBSA (molecular mechanics Poisson–Boltzmann surface area method). The computational analysis demonstrated these compounds could inhibit the enzyme. Nisoldipine had the strongest binding, and its complex was the most stable one. Furthermore, nicardipine was found to have the highest affinity toward the enzyme.

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“…They found that chemotherapy drugs inhibited the enzyme at low concentrations 19 . In a study by Gökçe et al 20 , they determined that salbutamol sulfate, tiotropium, varenicline tartrate, ciprofloxacin hydrochloride, fluticasone propionate, theophylline sodium glycinate, moxifloxacin hydrochloride, ampicillin trihydrate and montelukast sodium drugs strongly inhibited the PON1 enzyme. Salbutamol sulfate showed the strongest inhibitory effect, while montelukast sodium showed the weakest inhibition effect.…”

Section: Discussionmentioning

confidence: 99%

Investigation of Inhibition of Busulfan (Chemotherapeutic Drug) on Human Serum Paraoxonase-1 (PON1)

Söyüt¹

2021

International J. of Pharmacology

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Background and Objective: Paraoxonase 1 (PON1) is an antiatherogenic lactonase. It plays the role of an antioxidant enzyme by protecting HDLs from oxidative stress and also has important roles such as protection of Low-Density Lipoprotein (LDL) against oxidation and detoxification of highly toxic substances. Lowering the levels of this enzyme is a major risk in patients with cardiovascular disease. This study, it was aimed to investigate the in vitro effect of busulfan which is widely used in chemotherapy, on the human paraoxonase-1 enzyme. Materials and Methods: This study identifies interactions between the enzyme and busulfan, which is widely used in cancer chemotherapy. Paraoxonase activity measurement was used to determine the chemotherapeutic drug constants. Results: This study found that busulfan exhibited very potent inhibitory properties for human serum PON1 with an IC 50 value of 77 µM and an average K i value of 42.83 µM. Busulfan showed competitive inhibition. Conclusion: The use of busulfan, which has a very strong inhibition, in chemotherapeutic treatment can be very dangerous.

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Association of human serum paraoxonase‐1 with some respiratory drugs

Cited by 7 publications

References 30 publications

Evaluation of carbonic anhydrase and paraoxonase inhibition activities and molecular docking studies of highly water-soluble sulfonated phthalocyanines

Evaluation of carbonic anhydrase and paraoxonase inhibition activities and molecular docking studies of highly water-soluble sulfonated phthalocyanines

Evaluation of in vitro effect, molecular docking, and molecular dynamics simulations of some dihydropyridine‐class calcium channel blockers on human serum paraoxonase 1 (hPON1) enzyme activity

Investigation of Inhibition of Busulfan (Chemotherapeutic Drug) on Human Serum Paraoxonase-1 (PON1)

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