Synthesis of <i>N</i>‐alkylated pyrazolo[3,4‐<i>d</i>]pyrimidine analogs and evaluation of acetylcholinesterase and carbonic anhydrase inhibition properties

Aydın, Büşra; Anıl, Derya Aktaş; Demir, Yeliz

doi:10.1002/ardp.202000330

Cited by 35 publications

(21 citation statements)

References 55 publications

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“…The IC 50 values, which are the inhibitory concentration that reduces the enzyme activity by 50%, were calculated from activity (%) versus drugs plots 27,28 . To obtain K I , and inhibition types, three different inhibitory concentrations were used as described in our previous studies 29–31 …”

Section: Methodsmentioning

confidence: 99%

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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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Section: Methodsmentioning

confidence: 99%

“…27,28 To obtain K I , and inhibition types, three different inhibitory concentrations were used as described in our previous studies. [29][30][31]…”

Section: Biological Studiesmentioning

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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“…However, various sulfonamides unspecifically block all CA isoforms, which results in adverse side effects. The development of non-sulphonamide-based CAIs is necessary because a sizable section of the population cannot be treated with sulphonamides due to sulfa allergies [ 41 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel Bromophenol with Diaryl Methanes—Determination of Their Inhibition Effects on Carbonic Anhydrase and Acetylcholinesterase

et al. 2022

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In this work, nine new bromophenol derivatives were designed and synthesized. The alkylation reactions of (2-bromo-4,5-dimethoxyphenyl)methanol (7) with substituted benzenes 8–12 produced new diaryl methanes 13–17. Targeted bromophenol derivatives 18–21 were synthesized via the O-Me demethylation of diaryl methanes with BBr3. Moreover, the synthesized bromophenol compounds were tested with some metabolic enzymes such as acetylcholinesterase (AChE), carbonic anhydrase I (CA I), and II (CA II) isoenzymes. The novel synthesized bromophenol compounds showed Ki values that ranged from 2.53 ± 0.25 to 25.67 ± 4.58 nM against hCA I, from 1.63 ± 0.11 to 15.05 ± 1.07 nM against hCA II, and from 6.54 ± 1.03 to 24.86 ± 5.30 nM against AChE. The studied compounds in this work exhibited effective hCA isoenzyme and AChE enzyme inhibition effects. The results show that they can be used for the treatment of glaucoma, epilepsy, Parkinson’s as well as Alzheimer’s disease (AD) after some imperative pharmacological studies that would reveal their drug potential.

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“…[29,30] Generally, they are engaged in several key activities in all organisms the transport of CO 2 , fixation of CO 2 , ion balance and regulation of pH, respiration, and photosynthesis. [31,32] Therefore, for the management and treatment of tumors, obesity, glaucoma, epilepsy, and edema CA suppressors are employed. [33][34][35] Recently, CA isoenzymes have become an interesting biological target for the synthesis and design of potential inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Phthalimide‐tethered imidazolium salts: Synthesis, characterization, enzyme inhibitory properties, and in silico studies

Yiğit

Demir

Celepci

et al. 2022

Archiv der Pharmazie

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A series of new imidazolium salts were prepared in good yield by the reaction between 1-alkylimidazole and a variety of alkyl halides. The structures of the compounds were identified by FT-IR, 1 H NMR, and 13 C NMR spectroscopy, elemental analysis, and mass spectrometry. The crystal structure of 1b was determined by the single-crystal X-ray diffraction method. The phthalimidetethered imidazolium salts exhibited inhibition abilities toward acetylcholinesterase (AChE) and human carbonic anhydrases (hCAs) I and II, with K i values in the range of 24.63 ± 3.45 to 305.51 ± 35.98 nM for AChE, 33.56 ± 3.71 to 218.01 ± 25.21 nM for hCA I and 17.75 ± 0.96 to 308.67 ± 13.73 nM for hCA II. The results showed that the new imidazolium salts can play a key role in the treatment of Alzheimer's disease, epilepsy, glaucoma, and leukemia, which is related to their inhibition abilities of hCA I, hCA II, and AChE. Molecular docking and in silico absorption, distribution, metabolism, excretion and toxicity studies were used to look into how the imidazolium salts interacted with the specific protein targets. To better visualize and understand the binding positions and the influence of the imidazolium salts on hCA I, hCA II, and AChE conformations, each one was subjected to molecular docking simulations.

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Synthesis of N‐alkylated pyrazolo[3,4‐d]pyrimidine analogs and evaluation of acetylcholinesterase and carbonic anhydrase inhibition properties

Cited by 35 publications

References 55 publications

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

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

Synthesis of Novel Bromophenol with Diaryl Methanes—Determination of Their Inhibition Effects on Carbonic Anhydrase and Acetylcholinesterase

Phthalimide‐tethered imidazolium salts: Synthesis, characterization, enzyme inhibitory properties, and in silico studies

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