Synthesis and Cytotoxic Activity of New Thiazolopyrimidine Sugar Hydrazones and Their Derived Acyclic Nucleoside Analogues

Basiony, Ebtesam A.; Hassan, Allam A.; Alamshany, Zahra M.; Abdrabou, Ahmed; Abdel‐Rahman, Adel A.‐H.; Hassan, Nasser A.; El‐Sayed, Wael A.

doi:10.3390/molecules25020399

Cited by 19 publications

(8 citation statements)

References 50 publications

(56 reference statements)

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“…For the abovementioned benefits and as part of our program investigating syntheses of heterocyclic compounds which have biological significance [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ], herein, our focus will be on the synthesis, molecular docking and pharmacological evaluation of novel series of pyrazolo[4′,3′:5,6]pyrido[2,3- d ]pyrimidines and pyrazolo[4′,3′:5,6]pyrido[3,2- e ][1,2,4]triazolo[4,3- a ]pyrimidinone, which could serve as a promising scaffold in the development of novel viral protease inhibitors of SARS-CoV-2.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Molecular Docking Study of Novel Pyrimidine Derivatives against COVID-19

et al. 2023

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A novel series of pyrido[2,3-d]pyrimidines; pyrido[3,2-e][1,3,4]triazolo; and tetrazolo[1,5-c]pyrimidines were synthesized via different chemical transformations starting from pyrazolo[3,4-b]pyridin-6-yl)-N,N-dimethylcarbamimidic chloride 3b (prepared from the reaction of o-aminonitrile 1b and phosogen iminiumchloride). The structures of the newly synthesized compounds were elucidated based on spectroscopic data and elemental analyses. Designated compounds are subjected for molecular docking by using Auto Dock Vina software in order to evaluate the antiviral potency for the synthesized compounds against SARS-CoV-2 (2019-nCoV) main protease M pro. The antiviral activity against SARS-CoV-2 showed that tested compounds 7c, 7d, and 7e had the most promising antiviral activity with lower IC50 values compared to Lopinavir, “the commonly used protease inhibitor”. Both in silico and in vitro results are in agreement.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Molecular Docking Study of Novel Pyrimidine Derivatives against COVID-19

et al. 2023

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“…By incorporating donepezil-triazole with a sugar moiety, these compounds demonstrate the ability to effectively target and deliver drugs across the blood-brain barrier, allowing for potential therapeutic benefits in combating neurological conditions such as AD. Based on the insights from previously cited reports and our ongoing research in synthesizing biologically active compounds [41][42][43][44][45][46][47], we have successfully developed novel donepezil analogs by combining its precursor with a 1,2,3triazole core and diverse sugar/non-sugar components through click chemistry. These compounds were evaluated, aiming to enhance the potential for treating Alzheimer's disease effectively.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Molecular Docking and Biological Evaluation of Donepezil Analogues as Effective Anti-Alzheimer Agents.

Alshamari,

elsawalhy,

Alhajri

et al. 2023

Egypt. J. Chem.

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Discovering a cure for Alzheimer's disease remains an intricate endeavor. Acetylcholinesterase enzyme (AChE) inhibitors, such as donepezil, hold a crucial position in Alzheimer's therapy. Our present study focused on the innovative design and synthesis of new analogues of donepezil, employing a click chemistry approach. We characterized the molecular structures of these synthesized compounds through a combination of elemental analysis and various spectroscopic techniques, including FT-IR, 1 H NMR, and 13 C NMR methods. These substances underwent assessment to determine their ability to inhibit AChE activity. Most of the tested compounds demonstrated the capacity to effectively inhibit AChE. The in vitro experiments were utilized to determine the IC50 values for the most promising candidates, which were subsequently validated using molecular docking techniques. Interestingly, compound 15 displayed the best profile with IC50 of about IC50 = 0.392 μg/mL, in addition to its high docking score (-8.86 kcal/mol) and good in silico pharmacokinetic prediction. Therefore, 15 could be a promising compound that can be used for further development of novel drugs for Alzheimer's disease.

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“…Glycosides have also shown potential as protective candidates for AD treatment [28]. In our ongoing efforts to develop efficient methods for synthesizing medicinal heterocycles [29][30][31][32][33][34][35], we conducted a straightforward chemical reaction to create novel iminothiazolidinone derivatives using glucose isothiocyanate. These compounds, which share structural similarities with donepezil and acetylcholinesterase (AChE), could potentially act as AChE inhibitors, offering new possibilities for Alzheimer's disease (AD) treatment…”

Section: Introductionmentioning

confidence: 99%

Glycosyl Thiourea: Synthesis, Cyclization, Reaction, Molecular Docking, and Evaluation as Potential Acetylcholinesterase Inhibitors

Ellithy,

Abdel-Rahman,

Hassan

et al. 2023

Egypt. J. Chem.

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In this research, we successfully synthesized a distinctive group of iminothiazolidinone derivatives, using glucose isothiocyanate as the starting material. The structural elucidation of these newly created compounds was achieved through a combination of analytical techniques, including IR, 1 H NMR, and 13 C NMR. We then evaluated the inhibitory activity of these compounds against acetylcholinesterase (AChE) using the Ellman's method spectrophotometer, comparing their performance to standard drugs like donepezil, rivastigmine, and tacrine. Impressively, the majority of the tested compounds demonstrated inhibitory activity against AChE, with iminothiazolidinone derivative (5a) standing out as the most potent (IC 50 = 0.209 μg/mL). It even surpassed the effectiveness of rivastigmine and tacrine, coming close to the potency of donepezil. Further investigation into the potential of these compounds as AChE inhibitors for Alzheimer's disease drug development involved docking simulations using Molecular Operating Environment (MOE). Derivatives 3,5-disubstituted-(2,3,4,6-tetra-o-acetyl-β-Dglucopyranosyl) imino) thiazolidin-4-ones (5a), (5f), (6c) and 3,5-disubstituted-(β-D-glucopyranosyl)imino)thiazolidin-4-one (6d) displayed promising docking scores in MOE simulations. In Silico ADMET experiments assessed their pharmacokinetic and toxicity studies, demonstrating strong binding affinity and favorable interactions with the target protein. Pharmacophore models confirmed their potential as selective enzyme inhibitors through 3D virtual screening.

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Synthesis and Cytotoxic Activity of New Thiazolopyrimidine Sugar Hydrazones and Their Derived Acyclic Nucleoside Analogues

Cited by 19 publications

References 50 publications

Synthesis and Molecular Docking Study of Novel Pyrimidine Derivatives against COVID-19

Synthesis and Molecular Docking Study of Novel Pyrimidine Derivatives against COVID-19

Design, Synthesis, Molecular Docking and Biological Evaluation of Donepezil Analogues as Effective Anti-Alzheimer Agents.

Glycosyl Thiourea: Synthesis, Cyclization, Reaction, Molecular Docking, and Evaluation as Potential Acetylcholinesterase Inhibitors

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