Towards more effective acetylcholinesterase inhibitors: a comprehensive modelling study based on human acetylcholinesterase protein–drug complex

Ece, Abdulilah

doi:10.1080/07391102.2019.1583606

Cited by 50 publications

(25 citation statements)

References 55 publications

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“…The evaluation of the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of active compounds (ST1-11) was performed by QikProp software. [41] The computed parameters and their permissible values are summarized in Table 2. All predictions exhibited satisfactory values in terms of pharmacokinetic and physicochemical properties for novel ST1-11.…”

Section: Computational Studiesmentioning

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: Computational Studiesmentioning

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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“…Traditional methods for identification of inhibitors are expensive and time-consuming (Hou & Xu, 2004;Kolb & Sharpless, 2003;Mirza et al, 2019;Tahir ul Qamar et al, 2016;Xu, 2006). Therefore, the use of in silico techniques for identification of potential inhibitors has gained importance in recent years (Ece, 2020;Er et al, 2018;Mirza et al, 2019;Tahir ul Qamar et al, 2017;Tahir ul Qamar et al, 2019;. The available small molecule databases can be utilized for structure and ligand-based virtual screening to identify novel scaffolds that could serve as hits or leads to be optimized for enhanced activity (McInnes, 2007;Mumtaz et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Pharmacoinformatics and molecular dynamics simulation studies reveal potential covalent and FDA-approved inhibitors of SARS-CoV-2 main protease 3CL^pro

Alamri

Qamar

Mirza

et al. 2020

Journal of Biomolecular Structure and Dynamics

122

102

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The SARS-CoV-2 was confirmed to cause the global pandemic of coronavirus disease 2019 (COVID-19). The 3-chymotrypsin-like protease (3CLpro), an essential enzyme for viral replication, is a valid target to combat SARS-CoV and MERS-CoV. In this work, we present a structure-based study to identify potential covalent inhibitors containing a variety of chemical warheads. The targeted Asinex Focused Covalent (AFCL) library was screened based on different reaction types and potential covalent inhibitors were identified. In addition, we screened FDA-approved protease inhibitors to find candidates to be repurposed against SARS-CoV-2 3CLpro. A number of compounds with significant covalent docking scores were identified. These compounds were able to establish a covalent bond (C-S) with the reactive thiol group of Cys145 and to form favorable interactions with residues lining the substrate-binding site. Moreover, paritaprevir and simeprevir from FDA-approved protease inhibitors were identified as potential inhibitors of SARS-CoV-2 3CLpro. The mechanism and dynamic stability of binding between the identified compounds and SARS-CoV-2 3CLpro were characterized by molecular dynamics (MD) simulations. The identified compounds are potential inhibitors worthy of further development as COVID-19 drugs. Importantly, the identified FDA-approved anti-hepatitis-C virus (HCV) drugs paritaprevir and simeprevir could be ready for clinical trials to treat infected patients and help curb COVID-19.

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“…In case of QikProp predicted permeability through the monolayers of Madin−Darby Canine Kidney cells (QPPMDCK), past studies reported that ligands having <25 nm/sec score have poor MDCK cell permeability whereas ligands bearing >500 nm/sec QPPMDCK value shows great potential of being a drug-like molecule. Similarly, human oral absorption (HOA%) count in term of percentage should be preferably higher than 25% and to assess the bioavailability, polar absorption area of drug like compounds with ≤ 140Å 2 value are considered good for drug optimization [27].…”

Section: Drug-likeliness Analysismentioning

confidence: 99%

Synthesis, characterization, antituberculosis activity and computational studies on novel Schiff bases of 1,3,4-thiadiazole derivatives

Türk¹,

Karakuş²,

Maryam³

et al. 2020

jrp

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A series of novel Schiff bases were designed and synthesized by the condensation of 1,3,4-thiadiazoles that contain aromatic primary amine and variously substituted benzaldehydes. The synthesized compounds were screened for their antituberculosis activity against Mycobacterium tuberculosis H37Rv using BACTEC 460 radiometric system. Among the tested compounds, 2-(4-nitrophenyl)amino-5-[4-(3-(4-phenoxy))benzylideneaminophenyl]-1,3,4thiadiazole (3n) showed the highest inhibitory activity (80%). The activities of the newly synthesized Schiff bases were higher in comparison to those of intermediate products 2-(4-aminophenyl)-5-aryl/alkylamino-1,3,4thiadiazoles (2a-l). The computational studies were also performed to estimate drug-like profile of the compounds by using QikProp analysis.

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Towards more effective acetylcholinesterase inhibitors: a comprehensive modelling study based on human acetylcholinesterase protein–drug complex

Cited by 50 publications

References 55 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

Pharmacoinformatics and molecular dynamics simulation studies reveal potential covalent and FDA-approved inhibitors of SARS-CoV-2 main protease 3CL^pro

Synthesis, characterization, antituberculosis activity and computational studies on novel Schiff bases of 1,3,4-thiadiazole derivatives

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Towards more effective acetylcholinesterase inhibitors: a comprehensive modelling study based on human acetylcholinesterase protein–drug complex

Cited by 50 publications

References 55 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

Pharmacoinformatics and molecular dynamics simulation studies reveal potential covalent and FDA-approved inhibitors of SARS-CoV-2 main protease 3CLpro

Synthesis, characterization, antituberculosis activity and computational studies on novel Schiff bases of 1,3,4-thiadiazole derivatives

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Product

Resources

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Pharmacoinformatics and molecular dynamics simulation studies reveal potential covalent and FDA-approved inhibitors of SARS-CoV-2 main protease 3CL^pro