Computational drug repurposing of bethanidine for SENP1 inhibition in cardiovascular diseases treatment.

Abstract

AIMS:

Bethanidine (BW467C60) is a newly presented strong adrenergic neuron blocking factor which has a hypotensive operation in man. SENPs are essential for maintaining a balance between SUMOylation and deSUMOylation which can be disturbed by changing the expression of (sentrin-specific proteases) SENPs. SENP1 is the most studied isoform of SENPs. Hypertrophic stimuli can increase SENP1 expression using calcium/calcineurin-NFAT3 signaling in heart. Moreover, SENP1 expression may positively relate to the expression of mitochondrial genes of the heart, and can cause the heart and mitochondrial dysfunction.

MATERIALS AND METHODS:

In order to inhibit SENP1 using Bethanidine, molecular docking and molecular dynamics (MD) simulation of SENP1 with Bethanidine were performed. Molecular docking showed that Bethanidine can inhibit SENP1.

KEY FINDINGS:

MD Simulation showed that Bethanidine constitutes a stable complex with SENP1 as was evident from RMSD, RMSF, H-bond and DSSP plots. Free binding energy and the interaction patterns were obtained from molecular docking, and MD trajectory exhibited Bethanidine can be a potential drug candidate for SENP1 inhibition.

SIGNIFICANCE:

This study supplies enough evidences that Bethanidine is a potential inhibitor of SENP1 and can be applied for the treatment of cardiovascular diseases.

• Authors: Somayye Taghvaei, Zarrin Minuchehr, Farzaneh Sabouni
• Journal: Life sciences (Life Sci) Vol. 292 Pg. 120122 (Mar 01 2022) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 34748762 (Publication Type: Journal Article)
• Copyright: Copyright © 2021. Published by Elsevier Inc.

Chemical References

• SENP1 protein, human
• Cysteine Endopeptidases
• Bethanidine

Topics

• Bethanidine (chemistry)
• Cardiovascular Diseases (drug therapy)
• Cysteine Endopeptidases (chemistry)
• Humans
• Protein Binding
• Sumoylation