Exploration of stilbenoid trimers as potential inhibitors of sirtuin1 enzyme using a molecular docking and molecular dynamics simulation approach

Abdjan, Muhammad İkhlas; Aminah, Nanik Siti; Siswanto, Imam; Kristanti, Alfinda Novi; Takaya, Yoshiaki; Choudhary, M. Iqbal

doi:10.1039/d1ra02233d

Cited by 2 publications

(1 citation statement)

References 54 publications

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“…The redocking results showed an excellent superposition of 1NS with an RMSD value of 1.40 Å, which was supported by the previous report. [23] Furthermore, the docking process of DS1 and DS2 to the targeted protein occupied the SIRT1 binding site well. The scoring process used a grid score functional consisting of EvdW + Eele as the main contribution of the grid-score value (kcal/mol) in the gas term (Fig.…”

Section: Molecular Docking Analysismentioning

confidence: 94%

Pharmacokinetic, DFT Modeling, Molecular Docking, and Molecular Dynamics Simulation Approaches: Diptoindonesin A as a Potential Inhibitor of Sirtuin-1

Abdjan¹,

Aminah²,

Kristanti³

et al. 2022

Eng. Sci.

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Sirtuin 1 (SIRT1) is a class III histone deacetylase that regulates several cellular processes. SIRT1 overexpression is found in many cancer cases and is a potential therapeutic target. Unlike resveratrol, several stilbenoid dimers have been identified as SIRT1 inhibitors. This work studied the interaction and dynamic behavior of stilbenoid dimers and SIRT1. Prediction of binding free energy (∆Gbind) was calculated using the QM/MM-GBSA approach for each system, which resulted in 1NS-SIRT1: -21.44 kcal/mol, DS1-SIRT1: -25.94 kcal/mol, and DS2-SIRT1: -12.48 kcal/mol. These indicated that DS1 has a better chance as a SIRT1 inhibitor than DS2. The presence of glucose groups in DS1 potentially increased intermolecular interactions in the form of key residues and hydrogen bonds. Additionally, the quantum mechanical properties of DS1 and DS2 using the DFT/B3LYP/6-311++G(d,p) method were applied. The DS1 has three hydroxyls in the glucose group (3'-OH, 4'-OH, and 6'-OH) that could be reactive as nucleophiles and electrophiles. Furthermore, pharmacokinetic studies showcased the non-toxic properties of DS1.The analyses presented in this study could provide information on the quantum mechanical properties and inhibitory efficiency of stilbenoid dimers based on computational studies.

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Section: Molecular Docking Analysismentioning

confidence: 94%

Pharmacokinetic, DFT Modeling, Molecular Docking, and Molecular Dynamics Simulation Approaches: Diptoindonesin A as a Potential Inhibitor of Sirtuin-1

Abdjan¹,

Aminah²,

Kristanti³

et al. 2022

Eng. Sci.

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In Silico Identification and Evaluation of Natural Products as Potential Tumor Necrosis Factor Function Inhibitors Using Advanced Enalos Asclepios KNIME Nodes

Papadopoulou

Drakopoulos

Lagarias

et al. 2021

IJMS

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Tumor necrosis factor (TNF) is a regulator of several chronic inflammatory diseases, such as rheumatoid arthritis. Although anti-TNF biologics have been used in clinic, they render several drawbacks, such as patients’ progressive immunodeficiency and loss of response, high cost, and intravenous administration. In order to find new potential anti-TNF small molecule inhibitors, we employed an in silico approach, aiming to find natural products, analogs of Ampelopsin H, a compound that blocks the formation of TNF active trimer. Two out of nine commercially available compounds tested, Nepalensinol B and Miyabenol A, efficiently reduced TNF-induced cytotoxicity in L929 cells and production of chemokines in mice joints’ synovial fibroblasts, while Nepalensinol B also abolished TNF-TNFR1 binding in non-toxic concentrations. The binding mode of the compounds was further investigated by molecular dynamics and free energy calculation studies, using and advancing the Enalos Asclepios pipeline. Conclusively, we propose that Nepalensinol B, characterized by the lowest free energy of binding and by a higher number of hydrogen bonds with TNF, qualifies as a potential lead compound for TNF inhibitors’ drug development. Finally, the upgraded Enalos Asclepios pipeline can be used for improved identification of new therapeutics against TNF-mediated chronic inflammatory diseases, providing state-of-the-art insight on their binding mode.

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Exploration of stilbenoid trimers as potential inhibitors of sirtuin1 enzyme using a molecular docking and molecular dynamics simulation approach

Abstract: A combination of molecular docking and molecular dynamics simulation (250 ns) has been carried out to study the interaction of stilbenoid trimer compounds with the SIRT1 enzyme as the target protein.

Cited by 2 publications

References 54 publications

Pharmacokinetic, DFT Modeling, Molecular Docking, and Molecular Dynamics Simulation Approaches: Diptoindonesin A as a Potential Inhibitor of Sirtuin-1

Pharmacokinetic, DFT Modeling, Molecular Docking, and Molecular Dynamics Simulation Approaches: Diptoindonesin A as a Potential Inhibitor of Sirtuin-1

In Silico Identification and Evaluation of Natural Products as Potential Tumor Necrosis Factor Function Inhibitors Using Advanced Enalos Asclepios KNIME Nodes

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