Actinodaphnine and Rutacridone as New T-Cell Protein Tyrosine Phosphatase Inhibitors for Drug Development of Obesity

• Published in: IOP conference series. Materials Science and Engineering Vol. 546; no. 6; pp. 62007 - 62013
• Main Authors: Fitrianingrum, Y, Indarto, D, Kusumawati, R, Suselo, Y H
• Format: Journal Article
• Language: English
• Published: Bristol IOP Publishing 01.06.2019
• Subjects: Affinity; Binding; Bioinformatics; Inhibitors; Insulin; Ligands; Molecular conformation; Molecular docking; Obesity; Obesity treatment; Phosphatase; Phytochemicals; Proteins; Residues; Software; T-Cell Protein Tyrosine Phosphatase; Tyrosine
• ISSN: 1757-8981; 1757-899X
• DOI: 10.1088/1757-899X/546/6/062007

T-Cell Protein Tyrosine Phosphatase (TCPTP) is an obesogenic enzyme that inactivates a Signal Transducer and Activator Transcription 3 (STAT3) protein, leading to inhibition of leptin and insulin signalling. This protein can be a target for development of anti-obesity drugs. This study aimed to identify Indonesian phytochemicals as in silico TCPTP inhibitor. This bioinformatics study used a molecular docking method with AutoDock Vina software version 1.1.2. Three-dimensional structure of TCPTP protein and its Inhibitor (XIX, standard ligand) was obtained from Protein Data Bank (PDB) database with code 1L8K and PubChem database with code 9926586. Indonesian phytochemicals in this study were registered in the HerbalDB database and met criteria of Lipinski's rule. The three-dimensional structure of phytochemicals was obtained from PubChem National Center for Biotechnology Information (NCBI). Binding affinity and molecular conformation of selected Indonesian phytochemicals were assessed and compared to the standard ligand. PyMol version 1.3 software was used to visualize molecular docking results. Inhibitor XIX interacted with TCPTP protein at Gln125 and Thr129 residues with -6.30 kcal/mol binding affinity. Actinodaphnine and Rutacridone had lower binding affinity (-6.40 kcal / mol) than the standard ligand. Actinodaphnine interacted with the TCPTP protein at Thr129 and Asp130 residues while Rutacridone had interaction at Thr129 only. However, both phytochemicals had different conformation from PTP inhibitor XIX. Actinodaphnine is more potential to become a TCPTP inhibitor in silico for treatment of obesity than Rutacridone. Further investigation is required to evaluate the inhibitory effect of both phytochemicals towards the TCPTP protein.