MOLECULAR DYNAMICS SIMULATIONS OF SEVERAL SELECTED COMPOUNDS FROM THE HERBAL DATABASE OF INDONESIA RESULTS OF MOLECULAR DOCKING AGAINST DNA METHYLTRANSFERASE ENZYME

Authors

  • Muhamad Fikri Ihsan Department of Biomedical Computation, Faculty of Pharmacy, Universitas Indonesia, Depok, 16424, Indonesia.
  • Arry Yanuar Department of Biomedical Computation, Faculty of Pharmacy, Universitas Indonesia, Depok, 16424, Indonesia.

DOI:

https://doi.org/10.22159/ijap.2018.v10s1.63

Keywords:

Cancer, DNA Methyltransferase, Epigenetic, Herbal database Indonesia, Molecular dynamic simulation

Abstract

Objective: This study aimed to investigate the interactions of DNA methyltransferase (DNMT) enzymes and potential ligands as DNMT inhibitors
through molecular dynamics simulations.
Methods: This study was conducted using tools in the form of hardware (primary and secondary computers) and software (OpenBabel, AutoDock
Tools, Amber MD, Amber Tools, VMD, PuTTY, LigandScout, and UCSF Chimera).
Results: Results of molecular docking of cassiamin C, procyanidin B2, epicatechin-4alphaent-8-ent-epicatechin, epicatechin-4beta-8-epicatechin-
3-O-gallate, neorhusflavanone, 3-O-galloylepigallocatechin -4beta-6-epicatechin-3-O-gallate, withanolide, 3-O-galloylepigallocatechin-4beta-6-
epigallocatechin-3-O-gallate, cyanidin-3-6″-caffeylsophoroside-5-glucoside, epifriedelinol, gallocatechin-4alpha-8-epicatechin, scutellarein-7-
glucosyl-1-4-rhamnoside, epigallocatechin-3-gallate (EGCG) (positive control), and sinefungin (co-crystal) compounds showed ΔG values −9.34,
−10.95, −7.95, −11.01, −8.78, −8.87, −11.49, −7.98, −5.92, −8.92, −9.17, −8.76, −9.70, and −9.11 kcal/mol, respectively. Cassiamin C, procyanidin B2,
epicatechin-4-beta-8-epicatechin-3-O-gallate, withanolide, and gallocatechin-4alpha-8-epicatechin compounds had lower ΔG than sinefungin (cocrystal)
and EGCG (positive control) compounds. The results of molecular dynamic simulation of seven selected compounds showed the best overall
activities were procyanidin B2, epicatechin-4beta-8-epicatechin-3-O-gallate, and gallocatechin-4alpha-8-epi-catechin compounds.
Conclusions: The best overall activities based on molecular docking and molecular dynamic simulation were procyanidin B2, epicatechin-4beta-
8-epicatechin-3-O-gallate, and gallocatechin-4alpha-8-epi-catechin compounds. Amino acid residues that are important for the activity of DNMT1
inhibitor are Phe1145, Glu1168, Met1169, Cys1191, Glu1266, Ala1579, and Val1580.

Downloads

Download data is not yet available.

References

Maliya A. Cell changes Become Cancerous from the Point of View of

Molecular Biology. Vol. 1. Indonesia: Infokes; 2004. p. 1-7.

American Cancer Society. The History of Cancer. American Cancer

Society; 2014. p. 1-16. Available from: http://www.cancer.org/thehistory-

of-cancer-pdf. [Last accessed on 15 Sep 2016].

Luczak MW, Jagodziński PP. The role of DNA methylation in cancer

development. Folia Histochem Cytobiol 2006;44:143-54.

Mikeska T, Craig JM. DNA methylation biomarkers: Cancer and

beyond. Genes (Basel) 2014;5:821-64.

Lao TD, Le TA. Hypermethylated DNA as biomarker for nasopharyngeal

cancer detection. Asian J Pharm Clin Res 2018;11:68-71.

Wilakaputra IGNRB. Virtual Screenig of Indonesian Herbal Database

Inhibitor DNA Metiltransferase. Depok: Faculty of Pharmacy,

Universitas Indonesia; 2016.

Yoo CB, Jones PA. Epigenetic therapy of cancer: Past, present and

future. Nat Rev Drug Discov 2006;5:37-50.

Gnyszka A, Jastrzebski Z, Flis S. DNA methyltransferase inhibitors

and their emerging role in epigenetic therapy of cancer. Anticancer Res

;33:2989-96.

Rius M, Lyko F. Epigenetic cancer therapy: Rationales, targets and

drugs. Oncogene 2012;31:4257-65.

Lyko F, Brown R. DNA methyltransferase inhibitors and the

development of epigenetic cancer therapies. J Natl Cancer Inst

;97:1498-506.

Yen CY, Huang HW, Shu CW, Hou MF, Yuan SS, Wang HR, et al.

DNA methylation, histone acetylation and methylation of epigenetic

modifications as a therapeutic approach for cancers. Cancer Lett

;373:185-92.

Medina-Franco JL. Advances in computational approaches for

drug discovery based on natural products. Rev Latinoam Quim

;41:95-110.

Maldonado-Rojas W, Olivero-Verbel J, Marrero-Ponce Y.

Computational fishing of new DNA methyltransferase inhibitors from

natural products. J Mol Graph Model 2015;60:43-54.

Singh BN, Shankar S, Srivastava RK. Green tea catechin,

epigallocatechin-3-gallate (EGCG): Mechanisms, perspectives and

clinical applications. Biochem Pharmacol 2011;82:1807-21.

Gros C, Fahy J, Halby L, Dufau I, Erdmann A, Gregoire JM, et al.

DNA methylation inhibitors in cancer: Recent and future approaches.

Biochimie 2012;94:2280-96.

Shilpi A, Parbin S, Sengupta D, Kar S, Deb M, Rath SK, et al.

Mechanisms of DNA methyltransferase-inhibitor interactions:

Procyanidin B2 shows new promise for therapeutic intervention of

cancer. Chem Biol Interact 2015;233:122-38.

Published

20-12-2018

How to Cite

Ihsan, M. F., & Yanuar, A. (2018). MOLECULAR DYNAMICS SIMULATIONS OF SEVERAL SELECTED COMPOUNDS FROM THE HERBAL DATABASE OF INDONESIA RESULTS OF MOLECULAR DOCKING AGAINST DNA METHYLTRANSFERASE ENZYME. International Journal of Applied Pharmaceutics, 10(1), 285–290. https://doi.org/10.22159/ijap.2018.v10s1.63

Issue

Section

Original Article(s)

Most read articles by the same author(s)

<< < 1 2