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

Taghvaei, Somayye; Minuchehr, Zarrin; Sabouni, Farzaneh

doi:10.1016/j.lfs.2021.120122

Cited by 5 publications

(10 citation statements)

References 53 publications

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“…The docking operation was fulfilled in a grid box consisting of 60 × 60 × 60 (x, y, z) points at the center with 100 runs and the grid resolution of 0.375 Å to cover the SENP2 active site. Other parameters were set to default amounts (Taghvaei et al, 2021a;Taghvaei et al, 2021b). The best pose was selected for MD simulation.…”

Section: Protein and Ligand Preparationmentioning

confidence: 99%

“…MM-PBSA estimates the free energies and the scoring function in the computational drug design which is excessively applied to the survey of bio-molecular interactions (Kumari et al, 2014;Taghvaei et al, 2021a). The MM-PBSA mode was made in the GROMACS plan was used to compute the difference of the free energies (ΔG) among ligand configurations and free-SENP2.…”

Section: Molecular Mechanics-poisson Boltzmann Surface Areamentioning

confidence: 99%

“…The binding of a ligand to the protein can generally induce significant conformational alterations in the structure. The root mean square deviation (RMSD) parameter was computed to observe whether the structure of a protein is stable and near the experimental structure (Taghvaei et al, 2021a). The average RMSD value for free-SENP2, GA, CA, TQ, Betanin, Betanidin, Ebselen, and Fisetin were found to be 0.21, 0.23, 0.24, 0.17, 0.21, 0.23, 0.20, and 0.21 nm, respectively.…”

Section: Structural Deviations and Compactnessmentioning

confidence: 99%

“…The molecular identification between a protein and ligand is related to the hydrogen bonding pattern which supplies a specificity and directionality of interaction (Taghvaei et al, 2021a). We have computed hydrogen bonds pairing (within 0.35 nm) between SENP2 and ligands in the solvent condition.…”

Section: Hydrogen Bonds Analysismentioning

confidence: 99%

“…According to our previous studies on these secondary metabolites and observation of their anti-inflammatory and antioxidant effects in various cancer cell lines and the nervous system cells on SENP1 protein (Amiraslani et al, 2012;Alemi et al, 2013;Esmaeilzadeh et al, 2013;Rashid et al, 2019;Ahmadi et al, 2020;Taghvaei et al, 2021a;Taghvaei et al, 2021b) and considering that SENP2 protein is one of the factors involved in heart diseases, we suggested these compounds may also affect SENP2 and inhibition of SENP2 can be performed by these compounds to heart failure treatment (Kim et al, 2012;Chen et al, 2021).…”

Section: Introductionmentioning

confidence: 96%

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

2022

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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.

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Section: Protein and Ligand Preparationmentioning

confidence: 99%

Section: Molecular Mechanics-poisson Boltzmann Surface Areamentioning

confidence: 99%

Section: Structural Deviations and Compactnessmentioning

confidence: 99%

Section: Hydrogen Bonds Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

See 3 more Smart Citations

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

2022

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Function and regulation of ubiquitin-like SUMO system in heart

Wang,

Liu,

Bian

et al. 2023

Front. Cell Dev. Biol.

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The small ubiquitin-related modifier (SUMOylation) system is a conserved, reversible, post-translational protein modification pathway covalently attached to the lysine residues of proteins in eukaryotic cells, and SUMOylation is catalyzed by SUMO-specific activating enzyme (E1), binding enzyme (E2) and ligase (E3). Sentrin-specific proteases (SENPs) can cleave the isopeptide bond of a SUMO conjugate and catalyze the deSUMOylation reaction. SUMOylation can regulate the activity of proteins in many important cellular processes, including transcriptional regulation, cell cycle progression, signal transduction, DNA damage repair and protein stability. Biological experiments in vivo and in vitro have confirmed the key role of the SUMO conjugation/deconjugation system in energy metabolism, Ca2+ cycle homeostasis and protein quality control in cardiomyocytes. In this review, we summarized the research progress of the SUMO conjugation/deconjugation system and SUMOylation-mediated cardiac actions based on related studies published in recent years, and highlighted the further research areas to clarify the role of the SUMO system in the heart by using emerging technologies.

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Computational study of SENP1 in cancer by novel natural compounds and ZINC database screening

Taghvaei

Anvar

et al. 2023

Front. Pharmacol.

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Introduction: Sentrin-specific protease 1 (SENP1) is a protein whose main function is deSUMOylation. SENP1 inhibits apoptosis, and increases angiogenesis, estrogen and androgen receptor transcription and c-Jun transcription factor, proliferation, growth, cell migration, and invasion of cancer. The in vivo and in vitro studies also demonstrated which natural compounds, especially phytochemicals, minerals, and vitamins, prevent cancer. More than 3,000 plant species have been reported in modern medicine. Natural compounds have many anti-cancerous andanti-turmeric properties such as antioxidative, antiangiogenic, antiproliferative, and pro-apoptotic properties.Methods: In this study, we investigated the interaction of some natural compounds with SENP1 to inhibit its activity. We also screened the ZINC database including natural compounds. Molecular docking was performed, and toxicity of compounds was determined; then, molecular dynamics simulation (MDS) and essential dynamics (ED) were performed on natural compounds with higher free binding energies and minimal side effects. By searching in a large library, virtual screening of the ZINC database was performed using LibDock and CDOCKER, and the final top 20 compounds were allowed for docking against SENP1. According to the docking study, the top three leading molecules were selected and further analyzed by MDS and ED.Results: The results suggest that resveratrol (from the selected compounds) and ZINC33916875 (from the ZINC database) could be more promising SENP1 inhibitory ligands.Discussion: Because these compounds can inhibit SENP1 activity, then they can be novel candidates for cancer treatment. However, wet laboratory experiments are needed to validate their efficacy as SENP1 inhibitors.

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

Cited by 5 publications

References 53 publications

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

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

Function and regulation of ubiquitin-like SUMO system in heart

Computational study of SENP1 in cancer by novel natural compounds and ZINC database screening

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