Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Apr 1:13:817990.
doi: 10.3389/fphar.2022.817990. eCollection 2022.

Identification of Natural Products as SENP2 Inhibitors for Targeted Therapy in Heart Failure

Somayye Taghvaei  1 , Farzaneh Sabouni  1 , Zarrin Minuchehr  2
Affiliations

Identification of Natural Products as SENP2 Inhibitors for Targeted Therapy in Heart Failure

Somayye Taghvaei et al. Front Pharmacol. .

Abstract

Aims: Sentrin-specific protease -2 (SENP2) is involved in deSUMOylation. Increased deSUMOylation in murine hearts by SENP2 upregulation resulted in cardiac dysfunction and congenital heart defects. Natural compounds via regulating cell proliferation and survival, induce cell cycle cessation, cell death, apoptosis, and producing reactive oxygen species and various enzyme systems cause disease prevention. Then, natural compounds can be suitable inhibitors and since SENP2 is a protein involved in heart disease, so our aim was inhibition of SENP2 by natural products for heart disease treatment. Material and methods: Molecular docking and molecular dynamics simulation of natural products i.e. Gallic acid (GA), Caffeic acid (CA), Thymoquinone (TQ), Betanin, Betanidin, Fisetin, and Ebselen were done to evaluate the SENP2 inhibitory effect of these natural products. The toxicity of compounds was also predicted. Results: The results showed that Betanin constituted a stable complex with SENP2 active site as it revealed low RMSD, high binding energy, and hydrogen bonds. Further, as compared to Ebselen, Betanin demonstrated low toxicity, formed a stable complex with SENP2 via four to seven hydrogen bonds, and constituted more stable MD plots. Therefore, depending upon the outcomes presented herein, Betanin significantly inhibited SENP2 and hence may be considered as a suitable natural compound for the treatment of heart failure. Further clinical trials must be conducted to validate its use as a potential SENP2 inhibitor.

Keywords: SENP2; betanin; heart failure; molecular docking; molecular dynamics simulation; natural compounds.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
RMSD and RMSF plots of free-SENP2 and SENP2 complexes (black) free-SENP2, red) GA, green) CA, blue) TQ, yellow) Betanin, brown) Betanidin, gray) Ebselen, and purpule) Fisetin).
FIGURE 2
FIGURE 2
Rg, intramolecular hydrogen bonds, and SASA plots of SENP2 complexes, black) free-SENP2, red) GA, green) CA, blue) TQ, yellow) Betanin, brown) Betanidin, gray) Ebselen, and purple) Fisetin.
FIGURE 3
FIGURE 3
Intermolecular hydrogen bond plots of compounds (A) GA, (B) CA, (C) TQ, (D) Betanin, (E) Betanidin, (F) Ebselen, and (G) Fisetin.
FIGURE 4
FIGURE 4
Min distance between SENP2 and compounds (A) GA, (B) CA, (C) TQ, (D) Betanin, (E) Betanidin, (F) Ebselen, and (G) Fisetin.
FIGURE 5
FIGURE 5
Secondary structure plots of compounds (A) GA, (B) CA, (C) TQ, (D) Betanin, (E) Betanidin, (F) Ebselen, (G) Fisetin, and (H) free-SENP2.
FIGURE 6
FIGURE 6
Binding between Betanin, Betanidin, and Ebselen with SENP2 by Discovery Studio after molecular dynamics simulation (2D structures).
FIGURE 7
FIGURE 7
Binding between Betanin, Betanidin, and Ebselen with SENP2 by PyMOL after molecular dynamics simulation (3D structures).
FIGURE 8
FIGURE 8
Principal component analysis. Projection of the motion for compounds (red) GA, green) CA, blue) TQ, yellow) Betanin, brown) Betanidin, gray) Ebselen, purple) Fisetin, and black) free-SENP2. in phase space along the PC1 and PC2.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Abelson P. H. (1990). Medicine from Plants. Science 247 (4942), 513–514. 10.1126/science.2300807 - DOI - PubMed
    1. Abraham M. J., Van Der Spoel D., Lindahl E., Hess B. (2014). “The GROMACS Development Team” in GROMACS User Manual Version 5.0. KTH (Sweden: Royal Institute of Technology, Solna, Sweden and Uppsala University; ).
    1. Ahamad S., Kanipakam H., Birla S., Ali M. S., Gupta D. (2021). Screening Malaria-Box Compounds to Identify Potential Inhibitors against SARS-CoV-2 Mpro, Using Molecular Docking and Dynamics Simulation Studies. Eur. J. Pharmacol. 890, 173664. 10.1016/j.ejphar.2020.173664 - DOI - PMC - PubMed
    1. Ahmadi H., Nayeri Z., Minuchehr Z., Sabouni F., Mohammadi M. (2020). Betanin Purification from Red Beetroots and Evaluation of its Anti-oxidant and Anti-inflammatory Activity on LPS-Activated Microglial Cells. PloS one 15 (5), e0233088. 10.1371/journal.pone.0233088 - DOI - PMC - PubMed
    1. Albrow V. E., Ponder E. L., Fasci D., Békés M., Deu E., Salvesen G. S., et al. (2011). Development of Small Molecule Inhibitors and Probes of Human SUMO Deconjugating Proteases. Chem. Biol. 18 (6), 722–732. 10.1016/j.chembiol.2011.05.008 - DOI - PMC - PubMed

LinkOut - more resources