Molecular Docking Study of Substituted Chalcone Compounds as Potential Cyclin-Dependent Protein Kinase 2 (Cdk-2) Inhibitors

A series of 2-alkylamino-4-(3-coumarinyl)thiazoles were synthesized, characterized and evaluated their anticancer activity through molecular docking studies. Cell division protein kinase 2 (PDB code: 1KE9) is selected as a target and the compounds which obeys Lipinski rule of five is selected as a ligand. Molecular docking study is carried out using AutoDock Vina in PyRx virtual screening tool. This study revealed that all the compounds are active against the molecular target and compounds 5a and 5c have the highest docking score.

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Molecular docking and molecular dynamics simulation of anticancer active ligand ‘3,5,7,3′,5′-pentahydroxy-flavanonol-3-O-α-L-rhamnopyranoside’ from Bauhinia strychnifolia Craib to the cyclin-dependent protein kinase

Journal of King Saud University - Science ◽

10.1016/j.jksus.2019.05.004 ◽

2020 ◽

Vol 32 (1) ◽

pp. 891-895

Author(s):

Mohammad Ajmal Ali

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Molecular Dynamics Simulation ◽

Protein Kinase ◽

Dynamics Simulation ◽

Dependent Protein Kinase ◽

Active Ligand ◽

Dependent Protein

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Research on the Mechanism of Chuanxiong in Treating Diabetic Nephropathy by Network Pharmacology and Molecular Docking Technique

10.21203/rs.3.rs-1094538/v1 ◽

2021 ◽

Author(s):

Changyan Li ◽

Feng Su ◽

Le Zhang ◽

Fang Liu ◽

Zhen Li ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Molecular Docking ◽

Protein Kinase ◽

Steroid Hormone ◽

Active Components ◽

Dependent Protein Kinase ◽

Kegg Analysis ◽

Calcium Reabsorption ◽

Dependent Protein ◽

Angelica Lactone

Abstract Background Chuanxiong hort. It has been used in the clinic, but its main active components and drug mechanism are unknown. Objective To explore the mechanism of diabetic nephropathy (DN) treated with chuanxiong hort. Methods the active components and targets of chuanxiong Hort. were collected by TCPSP database, the DN gene expression data were collected by NCBI database, DN related genes were obtained by differential analysis. Furthermore, String and Cytoscape tools were used to construct the regulatory network of chuanxiong and the main active components for DN treatment. At the same time, PPI network interaction analysis was performed for core genes and GO. KEGG analysis was performed, prediction of molecular docking using Auto Dock Tools for critical genes. Results eight active components of chuanxiong Hort. were screened out, and one was recorded repeatedly. They were Angelica lactone A, ligusticum chuanxiong naphthofurolactone, Myricetin, 1-palmitic acid-2-linoleic acid-3-olein and ferulic acid ester of conifer. In addition, the active components interact with 15 disease targets, namely PGR, NR3C1, NCOA1, NCOA2, NR3C2, PTGS1, F2, F7, ESR1, AR, PPARG, ESR2, DPP4, HSP90AA1 and PRKACA. Besides, GO analysis of target genes, involved in the regulation of DN by chuanxiong Hort., were the regulation of cellular response to steroid hormone stimulation, the binding of nuclear receptors to steroid hormone receptors and the principle of cAMP-dependent protein kinase complexes. What's more, results of KEGG analysis showed that estrogen signalling pathway, endocrine and other factors-regulated calcium reabsorption and adipocyte adipogenesis played a role in the regulation of DN. Further molecular docking showed that NCOA1 and NCOA2 could interact with Angelica lactone A, Myricetin, Chrysophanol, chuanxiong naphthalize and Chrysophanol. Conclusion the active components of chuanxiong Hort., including Angelica Lactone A, Myricetin, Chrysophanol, chuanxiong naphthafunolide and Chrysophanol, can affect the regulation of estrogen signalling pathway, endocrine and other factors regulating calcium reabsorption and adipogenesis of adipocytes through the regulation of steroid hormone stimulation and regulation of cAMP-dependent protein kinase complex, and then play a therapeutic role on DN.

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Inhibition Mechanisms of Staurosporine and H7 to cAMP-Dependent Protein Kinase through Docking Study.

Chemical and Pharmaceutical Bulletin ◽

10.1248/cpb.44.618 ◽

1996 ◽

Vol 44 (3) ◽

pp. 618-620 ◽

Cited By ~ 4

Author(s):

Atsushi TAKAGI ◽

Miho YAMADA MIZUTANI ◽

Nobuo TOMIOKA ◽

Akiko ITAI

Keyword(s):

Protein Kinase ◽

Docking Study ◽

Dependent Protein Kinase ◽

Camp Dependent Protein Kinase ◽

Dependent Protein

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Computational Study of Novel Natural Inhibitors Targeting 3-Phosphoinositi-Dependent Protein Kinase 1(PDK1)

10.21203/rs.3.rs-579921/v1 ◽

2021 ◽

Author(s):

Sheng Zhong ◽

Zhen Guo ◽

Gaojing Dou ◽

Xiaye Lv ◽

Xinhui Wang ◽

...

Keyword(s):

Molecular Docking ◽

Protein Kinase ◽

Virtual Screening ◽

Binding Affinity ◽

Natural Environment ◽

Computational Study ◽

Dynamics Simulation ◽

Dependent Protein Kinase ◽

Lead Compounds ◽

Dependent Protein

Abstract Objective To screen ideal lead compounds with potential inhibition of 3-phosphoinositi-dependent protein kinase 1 (PDK1) from ZINC15 database, which is beneficial to drug design and improvement.Methods The Discovery Studio 4.5 computer-aided virtual screening technique was used to screen potential inhibitors of PDK1. Libdock was used for virtual screening and scoring of candidate compounds, ADME module was used for physical and chemical properties and toxicity analysis, and CDOCKER module was used for molecular docking analysis. The binding affinity of ligand-PDK1 was studied through molecular docking, and the stability of ligand-PDK1 in the natural environment was analyzed through molecular dynamics simulation.Results Two natural compounds ZINC00000157721 and ZINC000034189841 were screened from ZINC15 database. These two compounds have no CYP2D6 inhibition, easy to pass the blood-brain barrier, no hepatotoxicity, high binding affinity with PDK1, higher stability in the natural environment than positive drug BX-795, and stable existence.Conclusions The results show that ZINC00000157721 and ZINC000034189841 are ideal and safe lead compounds and have a potential inhibitory effect on PDK1. These compounds are safe candidates and may provide the basis and premise for the design and optimization of specific PDK1 inhibitors.

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