Usnic acid as potential inhibitors of BCL2 and P13K protein through network pharmacology-based analysis, molecular docking and molecular dynamic simulation

Wong, K K V; Roney, Miah; Uddin, Nazim; Imran, Syahrul; Gazali, Ahmad Mahfuz; Zamri, Normaiza; Rullah, Kamal; Aluwi, Mohd Fadhlizil Fasihi Mohd

doi:10.1080/07391102.2023.2178506

Cited by 7 publications

(2 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The RMSD elucidates the stability of docked complexes. [46][47][48] The average RMSD for MCULE-1255186442-0-1 (black), MCULE-4030371218-0-1 (red), and MCULE-7384556744-0-1 (green) with ADP-dependent DNA helicase RecQ was found 0.44 nm, 0.51, and 0.57 nm, respectively. The RMSD plot reveals that the stability of docked complex of protein and MCULE-1255186442-0-1 is the least as compared to the remaining two (Figure 4A).…”

Section: Root-mean-square Deviationmentioning

confidence: 99%

Identifying Potential Drug Candidates against Plasmodium falciparum (Isolate 3D7) through Targeting ADP-dependent DNA Helicase RecQ: An in silico Approach

Ahsan,

Mallick

2023

Ind. J. Pharm. Edu. Res

View full text Add to dashboard Cite

Background:The malarial scenario has significantly varied in the past few decades; whether it is funding or the range of sophisticated life-saving tools that have been improved, the disease burden has reduced, and even a few nations are on the verge of their elimination. Despite these, drug resistance is the major hurdle in the fight against malaria. Aim: Identifying new drug candidates with negligible toxicity are imperative to overcome the existing problem. The proposed study aims to identify new potential lead molecules via targeting the ADP-dependent DNA helicase RecQ of Plasmodium falciparum (isolate 3D7) using Target-Based Virtual Screening (TBVS), molecular docking, and dynamics simulations. Materials and Methods: Ligand molecules were retrieved from a comprehensive digital library of the MCULE database having millions of investigational compounds. Pfizer's rule of five and the number of halogen atoms (3-5) were considered the basic primary filters of TBVS. The AutoDockVina (ADV) and GROningenMAchine for Chemical Simulations software were used to assess the molecular interactions and stability of protein-ligand complexes, respectively. Results: The primary filters of the TBVS work-pipeline depicted 2,597,040 chemical hits from over a hundred million small molecules. The toxicity tool sifted twenty-one molecules whose HIA and BBB permeation were evaluated through the Egan-Egg model. Five ligand hits were shortlisted with zero violation of drug-likeness and contain three or more hydrogen bonds. ADME, docking, and MD parameters depicted a molecule MCULE-1255186442-0-1 as a promising drug candidate. Conclusion: Druggable properties of identified ligands are inferred purely from the in silico experiments, so before its therapeutic implications, wet-lab validations are imperative.

show abstract

Section: Root-mean-square Deviationmentioning

confidence: 99%

Identifying Potential Drug Candidates against Plasmodium falciparum (Isolate 3D7) through Targeting ADP-dependent DNA Helicase RecQ: An in silico Approach

Ahsan,

Mallick

2023

Ind. J. Pharm. Edu. Res

View full text Add to dashboard Cite

show abstract

“…In order to determine the efficiency of the ligand, MD simulation explains how atoms and molecules move over time and under specific conditions in a protein-ligand complex. 28,29 Following the post-simulation, principal component analysis (PCA) is used to evaluate the protein system's conformational variations and movement correlation. Molecular interactions of multi-components with the multiple targets of fibrosis can be explored by utilizing the network pharmacological computational methods.…”

Section: Introductionmentioning

confidence: 99%

Network pharmacology and in silico approaches to uncover multitargeted mechanism of action of Zingiber zerumbet rhizomes for the treatment of idiopathic pulmonary fibrosis

Byregowda,

Baby,

Maity

et al. 2024

F1000Res

View full text Add to dashboard Cite

Background Idiopathic pulmonary fibrosis (IPF) is a disease with high mortality, and there are only two specific drugs available for therapeutic management with limitations. The study aims to identify comprehensive therapeutic mechanisms of Zingiber zerumbet rhizomes (ZZR) to treat IPF by using network pharmacology followed battery of in silico studies. Methods The protein-protein interaction network was developed using Cytoscape to obtain core disease targets involved in IPF and their interactive molecules of ZZR. Based on the pharmacophore properties of phytomolecules from ZZR, the drug targets in IPF were explored. Protein-protein interaction network was built in Cytoscape to screen potential targets and components of ZZR. Molecular docking and dynamics were conducted as an empirical study to investigate the mechanism explored through network pharmacology in relation to the hub targets. Results The network analysis conferred kaempferol derivatives that had demonstrated a promising therapeutic effect on the perturbed, robust network hubs of TGF-β1, EGFR, TNF-α, MMP2 & MMP9 reported to alter the biological process of mesenchymal transition, myofibroblast proliferation, and cellular matrix deposition in pulmonary fibrosis. The phytomolecules of ZZR act on two major significant pathways, namely the TGF-β-signaling pathway and the FOXO-signaling pathway, to inhibit IPF. Confirmational molecular docking and dynamics simulation studies possessed good stability and interactions of the protein-ligand complexes by RMSD, RMSF, rGyr, SASA, and principal component analysis (PCA). Validated molecular docking and dynamics simulations provided new insight into exploring the mechanism and multi-target effect of ZZR to treat pulmonary fibrosis by restoring the alveolar phenotype through cellular networking. Conclusions Network pharmacology and in silico studies confirm the multitargeted activity of ZZR in the treatment of IPF. Further in vitro and in vivo studies are to be conducted to validate these findings.

show abstract

Comprehending the pharmacological mechanism of marine phenolic acids in bladder cancer therapy against matrix metalloproteinase 9 protein by integrated network pharmacology and in-silico approaches

Roney,

Uddin,

Fasihi Mohd Aluwi

2024

Computational Biology and Chemistry

View full text Add to dashboard Cite

Usnic acid as potential inhibitors of BCL2 and P13K protein through network pharmacology-based analysis, molecular docking and molecular dynamic simulation

Cited by 7 publications

References 43 publications

Identifying Potential Drug Candidates against Plasmodium falciparum (Isolate 3D7) through Targeting ADP-dependent DNA Helicase RecQ: An in silico Approach

Identifying Potential Drug Candidates against Plasmodium falciparum (Isolate 3D7) through Targeting ADP-dependent DNA Helicase RecQ: An in silico Approach

Network pharmacology and in silico approaches to uncover multitargeted mechanism of action of Zingiber zerumbet rhizomes for the treatment of idiopathic pulmonary fibrosis

Comprehending the pharmacological mechanism of marine phenolic acids in bladder cancer therapy against matrix metalloproteinase 9 protein by integrated network pharmacology and in-silico approaches

Contact Info

Product

Resources

About