Computational drug repurposing of bethanidine for SENP1 inhibition in cardiovascular diseases treatment
Life Sciences(2022)
摘要
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.
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关键词
SENP1 overexpression,Bethanidine,Molecular docking,Molecular dynamics simulation,Cardiovascular diseases
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