Inhibition profiles of Voriconazole against acetylcholinesterase, α‐glycosidase, and human carbonic anhydrase I and II isoenzymes

Topal, Fevzi

doi:10.1002/jbt.22385

Cited by 18 publications

(15 citation statements)

References 92 publications

(120 reference statements)

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“…Acetylcholinesterase (AChE), which is expressed in brain tissues and which operates to characterize ACh functioning in the central neural system alike in a balanced way, is a very efficient enzyme to hydrolyze ACh. [12][13][14][15][16] α-Glycosidase (α-GLY) as a glycoside hydrolase class, which hydrolyzes the α-glycosidic bonds in the carbohydrate molecules, [17] breaks the α-1,4-linked terminals of a sugar moiety. Also, it helps in the breakdown of carbohydrate molecules.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, characterization, biological evaluation, and in silico studies of novel 1,3‐diaryltriazene‐substituted sulfathiazole derivatives

Işık

Akocak

Lolak

et al. 2020

Archiv der Pharmazie

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In the present study, a series of eleven novel 1,3‐diaryltriazene‐substituted sulfathiazole moieties (ST1–11) was synthesized by the reaction of diazonium salt of sulfathiazole with substituted aromatic amines and their chemical structures were characterized by Fourier transform infrared, 1H‐NMR (nuclear magnetic resonance), 13C‐NMR, and high‐resolution mass spectroscopy methods. These synthesized novel derivatives were found to be effective inhibitor molecules for α‐glycosidase (α‐GLY), human carbonic anhydrase (hCA), and acetylcholinesterase (AChE), with KI values in the range of 426.84 ± 58.42–708.61 ± 122.67 nM for α‐GLY, 450.37 ± 50.35–1,094.34 ± 111.37 nM for hCA I, 504.37 ± 57.22–1,205.36 ± 195.47 nM for hCA II, and 68.28 ± 10.26–193.74 ± 19.75 nM for AChE. Among the synthesized novel compounds, several lead compounds were investigated against the tested metabolic enzymes. More specifically, ST11 (4‐[3‐(perfluorophenyl)triaz‐1‐en‐1‐yl]‐N‐(thiazol‐2‐yl)benzenesulfonamide) showed a highly efficient inhibition profile against hCA I, hCA II, and AChE, with KI values of 450.37 ± 50.35, 504.37 ± 57.22, and 68.28 ± 10.26 nM, respectively. Due to its significant biological inhibitory potency, this derivative may be considered as an interesting lead compound against these enzymes.

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Section: Introductionmentioning

confidence: 99%

Synthesis, characterization, biological evaluation, and in silico studies of novel 1,3‐diaryltriazene‐substituted sulfathiazole derivatives

Işık

Akocak

Lolak

et al. 2020

Archiv der Pharmazie

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“…The mechanism of inhibition and binding modes of the most potent anti‐BChE compound 4 p (IC 50 =2.87 μM) was determined by the Lineweaver‐Burke plot according to previous works [21,25] . As shown in Table 3 and Figure 3, the graphical analysis of the plot showed that with increasing concentration of compound 4 p , both the slopes (V max decreased) and intercepts (higher K m) were increased.…”

Section: Resultsmentioning

confidence: 98%

Fused 1,4‐Dihydropyridines and Their Corresponding Pyridines: Synthesis, Molecular Modeling and Cholinesterase Inhibition

et al. 2023

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Novel series of fused 1,4‐dihydropyridine derivatives were designed and synthesized. Oxidized to the corresponding pyridines were these dihydropyridines. Both dihydropyridines and pyridines were evaluated as acetyl and butyrylcholinesterase inhibitors. 1,4‐dihydropyridine derivatives outperformed pyridines against the butyrylcholinesterase enzyme, but none had a suitable inhibitory effect against acetylcholinesterase. Among the 1,4‐dihydropyridines, compounds derived from vanillin (4 j–p) inhibited butyrylcholinesterase (BChE) with IC50 values of 2.87–15.61 μM, but compounds derived from 4‐hydroxybenzaldehyde did not show a suitable inhibitory effect against butyrylcholinesterase. Among them, the compound 9‐(4‐((4‐Chlorobenzyl)oxy)‐3‐methoxyphenyl)‐3,4,6,7,9,10‐hexahydroacridine‐1,8(2H,5H)‐dione (4 p) showed appropriate inhibitory activity against BChE with an IC50 value of 2.87 μM compared with tacrine and donepezil as reference drugs (0.005 and 0.95 μM, respectively). The most outstanding results of kinetic and molecular modeling studies is that compound 4 p acts as a mixed and dual binding inhibitor, and binds to CAS and PAS of the BChE enzyme. These results show that with minor changes in the structure of fused 1,4‐dihydropyridines, new anti‐Alzheimer drugs with better performance can be achieved.

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“…In reports on drug interactions with voriconazole, a mixed inhibition of CYP enzymes in rat hepatic microsomes was reported when it was combined with vonoprazan, a reversible potassium-competitive acid blocker, which is metabolized by CYP2B6, CYP3A4, CYP2C19, and CYP2D6 [ 42 ]. In addition, voriconazole, although not a CYP enzyme, has shown non-competitive inhibition of human carbonic anhydrase 1 in its interaction with acetazolamide, and non-competitive inhibition of α-glycosidase in its interaction with acarbose, a drug used for reducing postprandial glucose in type 2 diabetes mellitus [ 43 ]. In the case of tofacitinib, when administered orally to healthy male adults, the AUC and C max of tofacitinib were 103% and 16% higher, respectively, when it was combined with ketoconazole, an imidazole antifungal drug, and its AUC and C max were 79% and 27% higher, respectively, when co-administered with fluconazole, a triazole antifungal drug [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Drug Interaction between Tofacitinib and Voriconazole in Rats

et al. 2021

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Fungal infections are prevalent in patients with immune diseases. Voriconazole, a triazole antifungal drug, inhibits the cytochromes CYP3A4 and CYP2C, and tofacitinib, a Janus kinase inhibitor for the treatment of rheumatoid arthritis, is metabolized by CYP3A4 and CYP2C19 in humans. Here, we investigated their interaction during simultaneous administration of both drugs to rats, either intravenously or orally. The area under the plasma concentration–time curve from time zero to time infinity (AUC) of tofacitinib was significantly greater, by 166% and 171%, respectively, and the time-averaged non-renal clearance (CLNR) of tofacitinib was significantly slower (59.5%) than that for tofacitinib alone. An in vitro metabolism study showed non-competitive inhibition of tofacitinib metabolism in the liver and intestine by voriconazole. The concentration/apparent inhibition constant (Ki) ratios of voriconazole were greater than two, indicating that the inhibition of tofacitinib metabolism could be due to the inhibition of the CYP3A1/2 and CYP2C11 enzymes by voriconazole. The pharmacokinetics of voriconazole were not affected by the co-administration of tofacitinib. In conclusion, the significantly greater AUC and slower CLNR of tofacitinib after intravenous and oral administration of both drugs were attributable to the non-competitive inhibition of tofacitinib metabolism via CYP3A1/2 and CYP2C11 by voriconazole in rats.

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Inhibition profiles of Voriconazole against acetylcholinesterase, α‐glycosidase, and human carbonic anhydrase I and II isoenzymes

Cited by 18 publications

References 92 publications

Synthesis, characterization, biological evaluation, and in silico studies of novel 1,3‐diaryltriazene‐substituted sulfathiazole derivatives

Synthesis, characterization, biological evaluation, and in silico studies of novel 1,3‐diaryltriazene‐substituted sulfathiazole derivatives

Fused 1,4‐Dihydropyridines and Their Corresponding Pyridines: Synthesis, Molecular Modeling and Cholinesterase Inhibition

Pharmacokinetic Drug Interaction between Tofacitinib and Voriconazole in Rats

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