In-silico Studies of Epoxy-Thioxanthone Derivatives as Potential Tyrosine Kinase Inhibitor Using Molecular Docking, Molecular Dynamics Simulations, MM-PBSA and ADMET

Hermawan, Faris and Jumina, Jumina and Pranowo, Harno Dwi and Ernawati, Teni and Kurniawan, Yehezkiel Steven and Kurniawan, Yehezkiel Steven and Zikri, Adi Tiara (2024) In-silico Studies of Epoxy-Thioxanthone Derivatives as Potential Tyrosine Kinase Inhibitor Using Molecular Docking, Molecular Dynamics Simulations, MM-PBSA and ADMET. Brazilian Journal of Pharmaceutical Sciences, 60: e23797. ISSN 19848250

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Abstract

Protein tyrosine kinases play a role in the cell signaling pathways involving cell growth, differentiation, apoptosis, and metabolism of cancer cells. Because of that, the molecular docking, molecular dynamics, MM-PBSA, and prediction ADMET properties were conducted to evaluate the inhibition activity of epoxy-thioxanthones against platelet-derived growth factors receptor (PDGFR) and epidermal growth factor receptor (EGFR) proteins. A series of ten thioxanthone compounds bearing hydroxy, epoxy, chloro, and bromo substituents have been designed and evaluated. The docking results showed that the epoxy-thioxanthones (A-J) have binding energy from-7.12 to-9.81 and-7.24 to-8.06 kcal/mol against those proteins, respectively. Compared with the native ligands, all epoxy-thioxanthones gave stronger binding energy (-7.24 to-8.06 kcal/mol) with the active site of EGFR than the erlotinib (-7.05 kcal/mol), which is remarkable. This result is also in line with the molecular dynamics results. The calculation of binding energy MM-PBSA that compounds D, E, I, and J had comparable EGFR protein stability to erlotinib. The binding energy of those compounds (-19.29 to-29.35 kcal/mol) had lower than erlotinib (-8.25 kcal/mol). Furthermore, in physicochemical properties prediction, those compounds fulfill Lipinski’s rule parameters and the minimum standard parameters in ADMET properties.

Item Type: Article
Uncontrolled Keywords: ADMET properties; EGFR; Epoxy thioxanthone; Molecular Docking; Molecular Dynamic; PDGFR
Subjects: Q Science > QD Chemistry
Divisions: Faculty of Mathematics and Natural Sciences > Chemistry Department
Depositing User: Masrumi Fathurrohmah
Date Deposited: 11 Mar 2025 07:45
Last Modified: 11 Mar 2025 07:45
URI: https://ir.lib.ugm.ac.id/id/eprint/15701

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