Computational study of imidazolylporphyrin derivatives as a radiopharmaceutical ligand for melanoma

Fransiska Kurniawan, Rahmana E. Kartasasmita, Naoki Yoshioka, Abdul Mutalib, Daryono H. Tjahjono

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Melanoma is the most aggressive type of skin cancer. Metastatic melanoma is extremely difficult to treat with current therapy methods such as surgery. On the other hand, it is a good opportunity to develop a radiopharmaceutical using a radionuclide such as Technetium (Tc) for diagnostic and Rhenium (Re) for therapeutic purposes. T3,4BCPP has been be used as a radioimaging agent for melanoma cancers experimentally. The aim of the present research was to design new imidazolylporphyrin derivatives with better selectivity and higher affinity than those of T3,4BCPP by molecular modeling. Methods: Eight types of Re-and Tc-labeled imidazolylporphyrins were docked to Fibroblast Growth Factor Receptor 1 (FGFR1, PDB ID: 5AM6) using AutoDock 4.2. FGFR1 was simulated by Molecular Dynamic (MD) simulation for 30 ns using NAMD 2.10 at 37 °C. The obtained conformations were then applied in a molecular docking simulation. Dovitinib (natural ligand of FGFR1), Re-and Tc-T3, 4BCPP were used as references. Results: The MD simulation resulted in an RMSD of 3.8 Å. From all the studied imidazolylporphyrin derivatives, Tc-cD3, 4BCPMIP and Re-cD3, 4BCPIP had the best docking parameter. Tc-cD3, 4BCPMIP had a free binding energy of 4.06 kcal/mol, while that of Re-cD3, 4BCPIP was 4.35 kcal/mol. Conclusion: It is concluded that cD3,4BCPMIP and cD3,4BCPIP are two potential candidate ligands for a melanoma radiopharmaceutical kit.

Original languageEnglish
Pages (from-to)191-199
Number of pages9
JournalCurrent Computer-Aided Drug Design
Volume14
Issue number3
DOIs
Publication statusPublished - 2018 Jan 1

Fingerprint

Rhenium
Radiopharmaceuticals
Technetium
Melanoma
Ligands
Molecular Dynamics Simulation
Molecular Docking Simulation
Receptor, Fibroblast Growth Factor, Type 1
Skin Neoplasms
Radioisotopes
Therapeutics
Research
Neoplasms

Keywords

  • FGF
  • Imidazolylporphyrin
  • Ligand
  • Melanoma
  • Molecular docking
  • Radiopharmaceutical

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Computational study of imidazolylporphyrin derivatives as a radiopharmaceutical ligand for melanoma. / Kurniawan, Fransiska; Kartasasmita, Rahmana E.; Yoshioka, Naoki; Mutalib, Abdul; Tjahjono, Daryono H.

In: Current Computer-Aided Drug Design, Vol. 14, No. 3, 01.01.2018, p. 191-199.

Research output: Contribution to journalArticle

Kurniawan, Fransiska ; Kartasasmita, Rahmana E. ; Yoshioka, Naoki ; Mutalib, Abdul ; Tjahjono, Daryono H. / Computational study of imidazolylporphyrin derivatives as a radiopharmaceutical ligand for melanoma. In: Current Computer-Aided Drug Design. 2018 ; Vol. 14, No. 3. pp. 191-199.
@article{a54c580462054080a3ef5a3eefcbba66,
title = "Computational study of imidazolylporphyrin derivatives as a radiopharmaceutical ligand for melanoma",
abstract = "Background: Melanoma is the most aggressive type of skin cancer. Metastatic melanoma is extremely difficult to treat with current therapy methods such as surgery. On the other hand, it is a good opportunity to develop a radiopharmaceutical using a radionuclide such as Technetium (Tc) for diagnostic and Rhenium (Re) for therapeutic purposes. T3,4BCPP has been be used as a radioimaging agent for melanoma cancers experimentally. The aim of the present research was to design new imidazolylporphyrin derivatives with better selectivity and higher affinity than those of T3,4BCPP by molecular modeling. Methods: Eight types of Re-and Tc-labeled imidazolylporphyrins were docked to Fibroblast Growth Factor Receptor 1 (FGFR1, PDB ID: 5AM6) using AutoDock 4.2. FGFR1 was simulated by Molecular Dynamic (MD) simulation for 30 ns using NAMD 2.10 at 37 °C. The obtained conformations were then applied in a molecular docking simulation. Dovitinib (natural ligand of FGFR1), Re-and Tc-T3, 4BCPP were used as references. Results: The MD simulation resulted in an RMSD of 3.8 {\AA}. From all the studied imidazolylporphyrin derivatives, Tc-cD3, 4BCPMIP and Re-cD3, 4BCPIP had the best docking parameter. Tc-cD3, 4BCPMIP had a free binding energy of 4.06 kcal/mol, while that of Re-cD3, 4BCPIP was 4.35 kcal/mol. Conclusion: It is concluded that cD3,4BCPMIP and cD3,4BCPIP are two potential candidate ligands for a melanoma radiopharmaceutical kit.",
keywords = "FGF, Imidazolylporphyrin, Ligand, Melanoma, Molecular docking, Radiopharmaceutical",
author = "Fransiska Kurniawan and Kartasasmita, {Rahmana E.} and Naoki Yoshioka and Abdul Mutalib and Tjahjono, {Daryono H.}",
year = "2018",
month = "1",
day = "1",
doi = "10.2174/1573409914666180417115248",
language = "English",
volume = "14",
pages = "191--199",
journal = "Current Computer-Aided Drug Design",
issn = "1573-4099",
publisher = "Bentham Science Publishers B.V.",
number = "3",

}

TY - JOUR

T1 - Computational study of imidazolylporphyrin derivatives as a radiopharmaceutical ligand for melanoma

AU - Kurniawan, Fransiska

AU - Kartasasmita, Rahmana E.

AU - Yoshioka, Naoki

AU - Mutalib, Abdul

AU - Tjahjono, Daryono H.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Melanoma is the most aggressive type of skin cancer. Metastatic melanoma is extremely difficult to treat with current therapy methods such as surgery. On the other hand, it is a good opportunity to develop a radiopharmaceutical using a radionuclide such as Technetium (Tc) for diagnostic and Rhenium (Re) for therapeutic purposes. T3,4BCPP has been be used as a radioimaging agent for melanoma cancers experimentally. The aim of the present research was to design new imidazolylporphyrin derivatives with better selectivity and higher affinity than those of T3,4BCPP by molecular modeling. Methods: Eight types of Re-and Tc-labeled imidazolylporphyrins were docked to Fibroblast Growth Factor Receptor 1 (FGFR1, PDB ID: 5AM6) using AutoDock 4.2. FGFR1 was simulated by Molecular Dynamic (MD) simulation for 30 ns using NAMD 2.10 at 37 °C. The obtained conformations were then applied in a molecular docking simulation. Dovitinib (natural ligand of FGFR1), Re-and Tc-T3, 4BCPP were used as references. Results: The MD simulation resulted in an RMSD of 3.8 Å. From all the studied imidazolylporphyrin derivatives, Tc-cD3, 4BCPMIP and Re-cD3, 4BCPIP had the best docking parameter. Tc-cD3, 4BCPMIP had a free binding energy of 4.06 kcal/mol, while that of Re-cD3, 4BCPIP was 4.35 kcal/mol. Conclusion: It is concluded that cD3,4BCPMIP and cD3,4BCPIP are two potential candidate ligands for a melanoma radiopharmaceutical kit.

AB - Background: Melanoma is the most aggressive type of skin cancer. Metastatic melanoma is extremely difficult to treat with current therapy methods such as surgery. On the other hand, it is a good opportunity to develop a radiopharmaceutical using a radionuclide such as Technetium (Tc) for diagnostic and Rhenium (Re) for therapeutic purposes. T3,4BCPP has been be used as a radioimaging agent for melanoma cancers experimentally. The aim of the present research was to design new imidazolylporphyrin derivatives with better selectivity and higher affinity than those of T3,4BCPP by molecular modeling. Methods: Eight types of Re-and Tc-labeled imidazolylporphyrins were docked to Fibroblast Growth Factor Receptor 1 (FGFR1, PDB ID: 5AM6) using AutoDock 4.2. FGFR1 was simulated by Molecular Dynamic (MD) simulation for 30 ns using NAMD 2.10 at 37 °C. The obtained conformations were then applied in a molecular docking simulation. Dovitinib (natural ligand of FGFR1), Re-and Tc-T3, 4BCPP were used as references. Results: The MD simulation resulted in an RMSD of 3.8 Å. From all the studied imidazolylporphyrin derivatives, Tc-cD3, 4BCPMIP and Re-cD3, 4BCPIP had the best docking parameter. Tc-cD3, 4BCPMIP had a free binding energy of 4.06 kcal/mol, while that of Re-cD3, 4BCPIP was 4.35 kcal/mol. Conclusion: It is concluded that cD3,4BCPMIP and cD3,4BCPIP are two potential candidate ligands for a melanoma radiopharmaceutical kit.

KW - FGF

KW - Imidazolylporphyrin

KW - Ligand

KW - Melanoma

KW - Molecular docking

KW - Radiopharmaceutical

UR - http://www.scopus.com/inward/record.url?scp=85051714270&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85051714270&partnerID=8YFLogxK

U2 - 10.2174/1573409914666180417115248

DO - 10.2174/1573409914666180417115248

M3 - Article

C2 - 29663897

AN - SCOPUS:85051714270

VL - 14

SP - 191

EP - 199

JO - Current Computer-Aided Drug Design

JF - Current Computer-Aided Drug Design

SN - 1573-4099

IS - 3

ER -