Synthesis, molecular docking, and in silico ADME prediction of some fused pyrazolo[1,5-a]pyrimidine and pyrazole derivatives as potential antimicrobial agents

Hassan, Ashraf S.; Morsy, Nesrin M.; Awad, Hassan M.

doi:10.1007/s13738-021-02319-4

Cited by 43 publications

(35 citation statements)

References 60 publications

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“…Additionally, the docking study illustrates the interaction between newly synthesized compounds and active sites in selected proteins at the atomic level to determine the behavior of new promising compounds in the binding site of the target proteins [ 29 ]. Furthermore, docking simulation studies have been progressed to visualize, calculate, formulate, and hypothesize about the energy and orientation of new ligands in the active site in the pocket of a target protein [ 30 , 31 ]. Our study involved docking of the most active derivative inside the RNA polymerase (RdRp) (PDB: 6m71) and spike glycoprotein (SGp) (PDB: 6VXX), and the results displayed good binding energy with lower binding affinity values (S) (kcal/mol) with different types of interactions and the docking results represented in Table 4 and Figure 6 , Figure 7 , Figure 8 and Figure 9 .…”

Section: Resultsmentioning

confidence: 99%

One-Pot Synthesis and Molecular Modeling Studies of New Bioactive Spiro-Oxindoles Based on Uracil Derivatives as SARS-CoV-2 Inhibitors Targeting RNA Polymerase and Spike Glycoprotein

El‐Kalyoubi

Ali

Seadawy³

et al. 2022

Pharmaceuticals

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The first outbreak in Wuhan, China, in December 2019 was reported about severe acute coronaviral syndrome 2 (SARS-CoV-2). The global coronavirus disease 2019 (COVID-19) pandemic in 2020 resulted in an extremely high potential for dissemination. No drugs are validated in large-scale studies for significant effectiveness in the clinical treatment of COVID-19 patients, despite the worsening trends of COVID-19. This study aims to design a simple and efficient cyclo-condensation reaction of 6-aminouracil derivatives 2a–e and isatin derivatives 1a-c to synthesize spiro-oxindoles 3a–d, 4a–e, and 5a–e. All compounds were tested in vitro against the SARS-CoV-2. Four spiro[indoline-3,5’-pyrido[2 ,3-d:6,5-d’]dipyrimidine derivatives 3a, 4b, 4d, and 4e showed high activities against the SARS-CoV-2 in plaque reduction assay and were subjected to further RNA-dependent-RNA-polymerase (RdRp) and spike glycoprotein inhibition assay investigations. The four compounds exhibited potent inhibitory activity ranging from 40.23 ± 0.09 to 44.90 ± 0.08 nM and 40.27 ± 0.17 to 44.83 ± 0.16 nM, respectively, when compared with chloroquine as a reference standard, which showed 45 ± 0.02 and 45 ± 0.06 nM against RdRp and spike glycoprotein, respectively. The computational study involving the docking studies of the binding mode inside two proteins ((RdRp) (PDB: 6m71), and (SGp) (PDB: 6VXX)) and geometrical optimization used to generate some molecular parameters were performed for the most active hybrids.

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Section: Resultsmentioning

confidence: 99%

One-Pot Synthesis and Molecular Modeling Studies of New Bioactive Spiro-Oxindoles Based on Uracil Derivatives as SARS-CoV-2 Inhibitors Targeting RNA Polymerase and Spike Glycoprotein

El‐Kalyoubi

Ali

Seadawy³

et al. 2022

Pharmaceuticals

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“…Pre-molecular docking simulations were completed using Molecular Operating Environmental (MOE) software version 2008.10 (Hassan et al, 2021 ; Ibrahim et al, 2021a , 2021b ). The docking processes for all drugs were performed according to the reported method (Fukuda et al, 2017 ) using the Triangle Matcher placement method and London dG as a scoring function.…”

Section: Methodsmentioning

confidence: 99%

Therapeutic strategies for Covid-19 based on molecular docking and dynamic studies to the ACE-2 receptors, Furin, and viral spike proteins

Khattab

Abol-Ftouh

Elhenawy

2021

Journal of Biomolecular Structure and Dynamics

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SARS-CoV-2 is a pandemic virus that caused infections and deaths in many world countries, including the Middle East. The virus-infected human cells by binding via ACE-2 receptor through the Spike protein of the virus with Furin's help causing cell membrane fusion leading to Covid-19-cell entry. No registered drugs or vaccines are triggering this pandemic viral disease yet. Our present work is based on molecular docking and dynamics simulation that performed to spike protein-ACE-2 interface complex, ACE-2 receptor, Spike protein (RBD), and Furin as targets for new small molecules. These drugs target new potential therapies to show their probabilities toward the active sites of mentioned proteins, strongly causing inhibition and/or potential therapy for covid-19. All target proteins were estimated against new target compounds under clinical trials and repurposing drugs currently present. Possibilities of those molecules and potential therapeutics acting on a certain target were predicted. MD simulations over 200 ns with molecular mechanics-generalized Born surface area (MMGBSA) binding energy calculations were performed. The structural and energetic analyses demonstrated the stability of the ligands-M Pros complex. Our present work will introduce new visions of some biologically active molecules for further studies in-vitro and in-vivo for Covid-19, repurposing of these molecules should be taking place under clinical works and offering different strategies for drugs repurposing against Covid-19 diseases. Communicated by Ramaswamy H. Sarma.

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“…Scheme 4 Synthesis of pyrimidine derivatives (13) from ß-formyl enamide Konakahara et al reported the synthesis of 4,5-disubstituted pyrimidine derivatives (17 ) via a ZnCl2-catalyzed threecomponents coupling reaction involving a variety of functionalized enamines (14 ), triethyl orthoformate (15 ), and ammonium acetate (16 ) [11] . Scheme 5 Synthesis of 4,5-disubstituted pyrimidine derivatives (17) Mosaad et al; prepared 6-amino-2-thioxo-2,3-dihydro-1H-pyrimidine-4-one (20 ) by the condensation of thiourea (18) with ethyl cyanoacetate (19 ) in sodium ethoxide [12]. Scheme 6 Synthesis of 6-amino-2-thioxo-2,3-dihydro-1H-pyrimidine-4-one (20) Ebtehal et al; reported the synthesis of 6-phenyl-2,4-disubstituted pyrimidine-5-carbonitriles (24) via prolonged heating of benzaldehyde (21), ethyl cyanoacetate (22 ) and thiourea (23 ) in ethanol, in the presence of potassium carbonate [13].…”

Section: Scheme 2 Synthesis Of Pyrimidine (7) From Uracilmentioning

confidence: 99%

An overview on synthesis and biological activity of pyrimidines

Mohamed¹,

Awad²,

El-tawab³

et al. 2022

World J. Adv. Res. Rev.

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Pyrimidines represent an important class of heterocycles containing two nitrogen atoms at position 1 and 3 of the six membered ring show wide range of biological activities. Numerous methods for the synthesis of pyrimidine and their diverse reactions offer enormous scope in the field of medicinal chemistry. Pyrimidine possesses wide spectrum of biological activities including antitubercular, antibacterial, antifungal, antiviral, anti-inflammatory, antimalarial, anticancer, and anti-HIV activity. The present review attempts to give brief information about the synthesis and various biological activities of pyrimidines and their derivatives.

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Synthesis, molecular docking, and in silico ADME prediction of some fused pyrazolo[1,5-a]pyrimidine and pyrazole derivatives as potential antimicrobial agents

Cited by 43 publications

References 60 publications

One-Pot Synthesis and Molecular Modeling Studies of New Bioactive Spiro-Oxindoles Based on Uracil Derivatives as SARS-CoV-2 Inhibitors Targeting RNA Polymerase and Spike Glycoprotein

One-Pot Synthesis and Molecular Modeling Studies of New Bioactive Spiro-Oxindoles Based on Uracil Derivatives as SARS-CoV-2 Inhibitors Targeting RNA Polymerase and Spike Glycoprotein

Therapeutic strategies for Covid-19 based on molecular docking and dynamic studies to the ACE-2 receptors, Furin, and viral spike proteins

An overview on synthesis and biological activity of pyrimidines

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