Design, synthesis, and SAR studies of novel 4-methoxyphenyl pyrazole and pyrimidine derivatives as potential dual tyrosine kinase inhibitors targeting both EGFR and VEGFR-2

El‐Naggar, Abeer M.; Hassan, Abdelfattah; Alesawy, Mohamed S; Al‐Karmalawy, Ahmed A.

doi:10.1016/j.bioorg.2022.105770

Cited by 69 publications

(35 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Depicting RMSD numbers below the 2.0 Å threshold would highlight the validity of the adopted docking protocol and ensure the biological significance of the obtained docking binding modes and so their respective scored energies. 54–57 Such a validation approach confirmed the ability of the adopted molecular modelling simulation protocol/procedures to replicate the co-crystallized ligand binding mode. Additionally, depicting low RMSD for the docked investigated ligands further validates the method highlighting the capability of these ligands to be complementary with the binding site topology and electrostatic surface in a fashion close to the co-crystallized ligand, which is of significant experimental inhibition activity data.…”

Section: Resultsmentioning

confidence: 67%

Quinoline–hydrazone hybrids as dual mutant EGFR inhibitors with promising metallic nanoparticle loading: rationalized design, synthesis, biological investigation and computational studies

et al. 2022

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 67%

Quinoline–hydrazone hybrids as dual mutant EGFR inhibitors with promising metallic nanoparticle loading: rationalized design, synthesis, biological investigation and computational studies

et al. 2022

View full text Add to dashboard Cite

show abstract

“…To ensure that the used force field was suitable for the docking process, the co-crystal ligand (O6K) was redocked within the SARS-CoV-2 M pro active site [ 42 , 43 , 44 , 45 ]. The obtained result showed that the docking procedure successfully regenerated the crystal pose with an RMSD value of 1.41 Å.…”

Section: Methodsmentioning

confidence: 99%

Anticoagulants as Potential SARS-CoV-2 Mpro Inhibitors for COVID-19 Patients: In Vitro, Molecular Docking, Molecular Dynamics, DFT, and SAR Studies

Elmaaty

Eldehna

Khattab

et al. 2022

IJMS

View full text Add to dashboard Cite

In this article, 34 anticoagulant drugs were screened in silico against the main protease (Mpro) of SARS-CoV-2 using molecular docking tools. Idraparinux, fondaparinux, eptifibatide, heparin, and ticagrelor demonstrated the highest binding affinities towards SARS-CoV-2 Mpro. A molecular dynamics study at 200 ns was also carried out for the most promising anticoagulants to provide insights into the dynamic and thermodynamic properties of promising compounds. Moreover, a quantum mechanical study was also conducted which helped us to attest to some of the molecular docking and dynamics findings. A biological evaluation (in vitro) of the most promising compounds was also performed by carrying out the MTT cytotoxicity assay and the crystal violet assay in order to assess inhibitory concentration 50 (IC50). It is worth noting that ticagrelor displayed the highest intrinsic potential for the inhibition of SARS-CoV-2 with an IC50 value of 5.60 µM and a safety index of 25.33. In addition, fondaparinux sodium and dabigatran showed promising inhibitory activities with IC50 values of 8.60 and 9.40 µM, respectively, and demonstrated safety indexes of 17.60 and 15.10, respectively. Moreover, the inhibitory potential of the SARS-CoV-2 Mpro enzyme was investigated by utilizing the SARS-CoV-2 Mpro assay and using tipranavir as a reference standard. Interestingly, promising SARS-CoV-2 Mpro inhibitory potential was attained for fondaparinux sodium with an IC50 value of 2.36 µM, surpassing the reference tipranavir (IC50 = 7.38 µM) by more than three-fold. Furthermore, highly eligible SARS-CoV-2 Mpro inhibitory potential was attained for dabigatran with an IC50 value of 10.59 µM. Finally, an SAR was discussed, counting on the findings of both in vitro and in silico approaches.

show abstract

“…Targeting specific components of the tumor extracellular matrix to normalize the tumor microenvironment has recently been proposed as a means to decompress tumor blood vessels, promote vascular perfusion, and hence improve drug delivery and cancer therapy efficacy [115] , [116] , [117] , [118] . As a result, the researchers set out to discover safe and well-tolerated pharmacological compounds that could modify the microenvironment of solid tumors [119] , [120] , [121] , [122] , [123] .…”

Section: Pharmacological Effects Of Pfdmentioning

confidence: 99%

Investigating the possible mechanisms of pirfenidone to be targeted as a promising anti-inflammatory, anti-fibrotic, anti-oxidant, anti-apoptotic, anti-tumor, and/or anti-SARS-CoV-2

Antar

Saleh²,

Al‐Karmalawy³

2022

Life Sciences

View full text Add to dashboard Cite

Design, synthesis, and SAR studies of novel 4-methoxyphenyl pyrazole and pyrimidine derivatives as potential dual tyrosine kinase inhibitors targeting both EGFR and VEGFR-2

Cited by 69 publications

References 75 publications

Quinoline–hydrazone hybrids as dual mutant EGFR inhibitors with promising metallic nanoparticle loading: rationalized design, synthesis, biological investigation and computational studies

Quinoline–hydrazone hybrids as dual mutant EGFR inhibitors with promising metallic nanoparticle loading: rationalized design, synthesis, biological investigation and computational studies

Anticoagulants as Potential SARS-CoV-2 Mpro Inhibitors for COVID-19 Patients: In Vitro, Molecular Docking, Molecular Dynamics, DFT, and SAR Studies

Investigating the possible mechanisms of pirfenidone to be targeted as a promising anti-inflammatory, anti-fibrotic, anti-oxidant, anti-apoptotic, anti-tumor, and/or anti-SARS-CoV-2

Contact Info

Product

Resources

About