scholarly journals Identification of PRMT5 Inhibitors with Novel Scaffold Structures through Virtual Screening and Biological Evaluations

2021 ◽  
Author(s):  
Lun Zhang ◽  
Chenxi Cao ◽  
Jia Jin ◽  
Yaohua Fan ◽  
Xiaoguang Wang ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Md Simulations ◽  
Leukemia Cells ◽  
Moderate Activity ◽  
Arginine Methyltransferase ◽  
Docking Analysis ◽  
Cycle Arrest ◽  
Anticancer Target ◽  
Novel Scaffold ◽  
Molecular Docking Analysis

Abstract Protein arginine methyltransferase 5 (PRMT5), an important member in PRMT family, has been validated as a promising anticancer target. In this study, through the combination of virtual screening and biological experiments, we have identified two PRMT5 inhibitors with novel scaffold structures. Among them, compound Y2431 showed moderate activity with IC50 value of 10.09 μM and displayed good selectivity against other methyltransferases. The molecular docking analysis and molecular dynamics (MD) simulations suggested that the compound occupied the substrate-arginine binding site. Furthermore, Y2431 exhibited anti-proliferative activity to leukemia cells by inducing cell cycle arrest. Overall, the hit compound could provide a novel scaffold for further optimization of small-molecule PRMT5 inhibitors.

scholarly journals Identification of Novel Inhibitors against Coactivator Associated Arginine Methyltransferase 1 Based on Virtual Screening and Biological Assays

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Fei Ye ◽  
Weiyao Zhang ◽  
Wenchao Lu ◽  
Yiqian Xie ◽  
Hao Jiang ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Small Molecule ◽  
Protein Interactions ◽  
Binding Mode ◽  
Protein Protein Interactions ◽  
Arginine Methyltransferase ◽  
Docking Analysis ◽  
Biological Assays ◽  
Biochemical Assays ◽  
Methyltransferase 1

Overexpression of coactivator associated arginine methyltransferase 1 (CARM1), a protein arginine N-methyltransferase (PRMT) family enzyme, is associated with various diseases including cancers. Consequently, the development of small-molecule inhibitors targeting PRMTs has significant value for both research and therapeutic purposes. In this study, together with structure-based virtual screening with biochemical assays, two compounds DC_C11 and DC_C66 were identified as novel inhibitors of CARM1. Cellular studies revealed that the two inhibitors are cell membrane permeable and effectively blocked proliferation of cancer cells including HELA, K562, and MCF7. We further predicted the binding mode of these inhibitors through molecular docking analysis, which indicated that the inhibitors competitively occupied the binding site of the substrate and destroyed the protein-protein interactions between CARM1 and its substrates. Overall, this study has shed light on the development of small-molecule CARM1 inhibitors with novel scaffolds.

scholarly journals Identification of Potential Dipeptidyl Peptidase (DPP)-IV Inhibitors among Moringa oleifera Phytochemicals by Virtual Screening, Molecular Docking Analysis, ADME/T-Based Prediction, and In Vitro Analyses

Molecules ◽  
2020 ◽  
Vol 25 (1) ◽  
pp. 189 ◽  
Author(s):  
Yang Yang ◽  
Chong-Yin Shi ◽  
Jing Xie ◽  
Jia-He Dai ◽  
Shui-Lian He ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Moringa Oleifera ◽  
Molecular Mechanisms ◽  
Dipeptidyl Peptidase ◽  
In Vivo Evaluation ◽  
Docking Analysis ◽  
Dpp Iv ◽  
Molecular Docking Analysis

Moringa oleifera Lam. (MO) is called the “Miracle Tree” because of its extensive pharmacological activity. In addition to being an important food, it has also been used for a long time in traditional medicine in Asia for the treatment of chronic diseases such as diabetes and obesity. In this study, by constructing a library of MO phytochemical structures and using Discovery Studio software, compounds were subjected to virtual screening and molecular docking experiments related to their inhibition of dipeptidyl peptidase (DPP-IV), an important target for the treatment of type 2 diabetes. After the four-step screening process, involving screening for drug-like compounds, predicting the absorption, distribution, metabolism, excretion, and toxicity (ADME/T) of pharmacokinetic properties, LibDock heatmap matching analysis, and CDOCKER molecular docking analysis, three MO components that were candidate DPP-IV inhibitors were identified and their docking modes were analyzed. In vitro activity verification showed that all three MO components had certain DPP-IV inhibitory activities, of which O-Ethyl-4-[(α-l-rhamnosyloxy)-benzyl] carbamate (compound 1) had the highest activity (half-maximal inhibitory concentration [IC50] = 798 nM). This study provides a reference for exploring the molecular mechanisms underlying the anti-diabetic activity of MO. The obtained DPP-IV inhibitors could be used for structural optimization and in-depth in vivo evaluation.

scholarly journals PHARMACOINFORMATICS APPROACH OF IDENTIFIED BIOLOGICAL COMPOUNDS FROM SELECTED PLECTRANTHUS (L.) SPECIES IN TAMIL NADU, INDIA: AN IN-SILICO APPROACH

2021 ◽  
Vol 12 (7) ◽  
pp. 14-21
Author(s):  
Selvarasuvasuki Manikandan ◽  
Sabeerali Ansarali ◽  
Manikandan Priyadharshini ◽  
Ganapathy Murugan Alagu Lakshmanan
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Tamil Nadu ◽  
Biological Activities ◽  
Ligand Interaction ◽  
Docking Analysis ◽  
Biological Compounds ◽  
Low Toxicity ◽  
Plectranthus Amboinicus ◽  
Molecular Docking Analysis

Aim: Plectranthus (Linn) is a typical genus of the Indian flora. It had been used in the folk medicines for its several medicinal properties. In this study, there are twenty-five major biological compounds were selected from Plectranthus forskohlii, Plectranthus coleoides, Plectranthus rotundifolius and Plectranthus vettiveroides for molecular docking analysis and find out the active compounds against Diabetic, Cancer and Tuberculosis diseases. Materials and methods: Biological compounds of Plectranthus Species were identifying and investigated by GC-MS and the biological activities of these compounds were studied with virtual screening, ADMET analysis, Protein ligand interaction through molecular docking analysis. Results: Twenty-five major biological compounds were selected for virtual screening analysis to find out the drug likeness activity. Out of these twenty-five compounds nine compounds are drug likeness in nature. Based on the ADMET analysis, Thymol beta D-Glucoside showed the low toxicity level and it represent Lipinski rule of five. The molecular docking results of Thymol beta D-Glucoside interact with different target proteins used in the study showed the maximum docking energy was obtained against tuberculosis protein -10.1846kcal/mol followed by diabetic protein -10.8736kcal/mol and cancer protein -11.4109kcal/mol. Conclusion: Plectranthus amboinicus leaves showed significant anti-diabetic, anti-cancer, anti-tuberculosis activity when compared to other studied species such as Plectranthus forskohlii, Plectranthus coleoides, Plectranthus rotundifolius and Plectranthus vettiveroides.

scholarly journals In Silico Molecular Docking Analysis of Natural Pyridoacridines as Anticancer Agents

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Vikas Sharma ◽  
Prabodh Chander Sharma ◽  
Vipin Kumar
Keyword(s):  
Cell Cycle ◽  
Anticancer Agents ◽  
Molecular Targets ◽  
Structural Diversity ◽  
Docking Studies ◽  
Docking Analysis ◽  
Anticancer Target ◽  
In Silico Molecular Docking ◽  
Near Future ◽  
Molecular Docking Analysis

Docking studies are proved to be an essential tool that facilitates the structural diversity of natural products to be harnessed in an organized manner. In this study, pyridoacridines containing natural anticancer pigments were subjected to docking studies using Glide (Schrodinger). Investigations were carried out to find out the potential molecular targets for these selected pigments. The docking was carried out on different cancer macromolecules involved in different cell cycle pathways, that is, CDK-2, CDK-6, Bcl-2, VEGFR-2, IGF-1R kinase, and G-Quadruplexes. CDK-6 was found to be the most suitable anticancer target for the pyridoacridines. In addition, effectiveness of the study was further evaluated by performing docking of known inhibitors against their respective selected macromolecules. However, the results are preliminary and experimental evaluation will be carried out in near future.

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