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
![[thumbnail of 2.938 Insilico-Studies-of-EpoxyThioxanthone-Derivatives-as-Potential-Tyrosine-Kinase-Inhibitor-Using-Molecular-Docking-Molecular-Dynamics-Simulations-MMPBSA-and-ADMETBrazilian-Journal-of-Pharmaceutical-Sciences.pdf]](https://ir.lib.ugm.ac.id/style/images/fileicons/text.png)
2.938 Insilico-Studies-of-EpoxyThioxanthone-Derivatives-as-Potential-Tyrosine-Kinase-Inhibitor-Using-Molecular-Docking-Molecular-Dynamics-Simulations-MMPBSA-and-ADMETBrazilian-Journal-of-Pharmaceutical-Sciences.pdf - Published Version
Restricted to Registered users only
Download (1MB) | Request a copy
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 |