Molecular Docking Studies of a Chalcone Derivative Compound p-hydroxy-m-methoxychalcone with Tyrosine Kinase Receptors

Background: Electrophilic compounds bearing Michael acceptors present great promise in anticancer drug discovery. Methods: Drawing inspirations from cytotoxic Piper lactam alkaloids, twelve N-acylated butyro- and valerolactams were prepared and evaluated for antiproliferative and cytotoxic activities against the normal human umbilical vein endothelial cells (HUVEC), chronic human myeloid leukemia cells (K- 562), and Henrietta Lacks (HeLa) cells used as model cell lines. Molecular docking of bioactive derivatives was performed against tyrosine kinase. Results: Results of the MTT assay showed the crotonylated (5) and nitro-containing cinnamoyl (8) butyrolactams, and, the crotonylated (10), trifluoromethylated (13), and chlorinated (14) cinnamoyl valerolactam derivatives as the most antiproliferative against human myeloid leukemia cells. The trifluoromethylated cinnamoyl valerolactam (13) displayed the best selectivity on K-562 cells. Molecular docking studies of 13 against tyrosine kinase provided evidence as tyrosine kinase inhibitor, having comparable binding energy and receptor interaction with imatinib. Conclusion: The presence of electrophilic N-acrylic moieties contributes to the potential of a compound as inspiration to develop anti-leukemia drugs.

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Searching for Potential Novel BCR-ABL Tyrosine Kinase Inhibitors Through G-QSAR and Docking Studies of Some Novel 2-Phenazinamine Derivatives

Current Computer - Aided Drug Design ◽

10.2174/1573409914666181022142934 ◽

2020 ◽

Vol 16 (5) ◽

pp. 501-510

Author(s):

Mayura Kale ◽

Gajanan Sonwane ◽

Yogesh Choudhari

Keyword(s):

Molecular Docking ◽

Tyrosine Kinase ◽

Anticancer Activity ◽

Statistical Significance ◽

External Validation ◽

Docking Studies ◽

Binding Interactions ◽

Standard Drug ◽

Molecular Docking Studies ◽

Abl Tyrosine Kinase

Background: The computational studies on 2-phenazinamines with their protein targets have been carried out to design compounds with potential anticancer activity and selectivity over specific BCR-ABL Tyrosine kinase. Methods: This has been achieved through G-QSAR and molecular docking studies. Computational chemistry was done by using VLife MDS 4.3 and Autodock 4.2. 2D and structures of ligands were drawn by using Chemdraw 2D Ultra 8.0 and were converted into 3D. These were optimized by using semi-empirical method called MOPAC. The protein structure was downloaded as PDB file from RCSC protein data bank. PYMOL was used for studying the binding interactions. The G-QSAR models generated were found to possess training (r2=0.8074), cross-validation (q2=0.6521), and external validation (pred_r2=0.5892) which proved their statistical significance. Accordingly, the newly designed series of 2-phenazinamines viz., 3-chloro-4-aryl-1-(phenazin-7-yl) azetidin-2-ones (4a-4e) were subjected to wet lab synthesis. Alternatively, docking st udies were also conducted which showed binding interactions of some derivatives with > 30% higher binding energy values than the standard anticancer drug imatinib. The lower energy values obtained for these derivatives indicate energetically favorable interaction with protein binding site as compared to standard imatinib. Results: G-QSAR and molecular docking studies predicted better anticancer activity for the synthesized azitidine derivatives of 2-phenazinamines (4a-4e) as compared to standard drug. Conclusion: It is therefore surmised that the molecular manipulations at appropriate sites of these derivatives suggested by structure activity relationship data will prove to be beneficial in raising anticancer potential.

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In Silico Screening of Potential Inhibitors of the Epidermal Growth Factor Receptor Kinase using Benzimidazole, Benzoxazole, Imidazole, and Tetrazole Derivatives

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i50b33428 ◽

2021 ◽

pp. 60-71

Author(s):

Subramaniyan Arulmurugan ◽

Helen P. Kavitha ◽

Jasmine P. Vennila

Keyword(s):

Molecular Docking ◽

Tyrosine Kinase ◽

In Silico ◽

Heterocyclic Compounds ◽

Docking Studies ◽

Tyrosine Kinase Receptor ◽

Binding Interaction ◽

Docking Score ◽

Molecular Docking Studies ◽

Egfr Tyrosine Kinase

Background: Small molecule compounds are docked into receptor binding sites and the binding affinity of the complex is calculated using the structure-based drug design technique. Precise and quick docking processes, as well as the capacity to examine binding geometries and interactions, are required for a full knowledge of the structural principles that influence the strength of a protein/ligand complex. The present work deals with in-silico molecular docking studies of some heterocyclic compounds such as benzoxazole, benzimidazole, imidazole and tetrazole against the EGFR tyrosine kinase receptor. Methodology: Molecular docking studies of some heterocyclic compounds such as benzoxazole, benzimidazole, imidazole and tetrazole against the EGFR tyrosine kinase receptor using Schrodinger LLC (Maestro 9.2) software. Results: Our in silico observations reveal that, all the selected heterocyclic compounds (1-8) show good binding interaction and good docking score against selected target enzyme. Out of eight compounds selected for the study two compounds compound 3 and 7 shows higher glide score. Compound 3 binded to ASP855 with a docking score of −11.20 kcal/mol. Compound 7 binded to ASP855 with a docking score of −11.56kcal/mol. Conclusion: Docking results revealed that compounds (1-8) interact with EGFR kinase receptor active site. Among the compounds, compound 7 has shown the highest glide score of -11.56 kcal/mol.

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