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DNA Methyltransferases Directed Anti-Cancerous Plant Medicine (Xanthomicrol and Galloyl) Based Molecular Docking and Dynamics Simulation

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DOI: 10.4236/cmb.2015.52003    2,561 Downloads   2,988 Views   Citations

ABSTRACT

DNA methyltransferases 1 (DNMT1) has been looked as crucial targets against various types of cancers. MD simulations have advanced to a point where the atomic level information of biological macromolecule (protein or DNA-protein or protein-protein) can easily be advantageous to predict the functionality. In this study we utilize xanthomicrol and galloyl compounds to investigate potential compounds for the inhibition of DNMT1, and the results of these two compounds are compared with drug decitabine. Xanthomicrol and galloyl are found to dock successfully within the active site of DNMT1. A comparison of the inhibitory potential of screened xanthomicrol inhibited DNMT1 approximately is identical with those of their corresponding drugs, decitabine. The stability of the DNMT1 with the best docked xanthomicrol, were further analysed in molecular dynamics (MD) simulation and compared with those of the respective drugs namely decitabine which revealed stabilization of these complexes within 300 ns of simulation with better stability of DNMT1.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Soureshjani, E. , Babaheydari, A. and Saberi, E. (2015) DNA Methyltransferases Directed Anti-Cancerous Plant Medicine (Xanthomicrol and Galloyl) Based Molecular Docking and Dynamics Simulation. Computational Molecular Bioscience, 5, 13-19. doi: 10.4236/cmb.2015.52003.

References

[1] Bird, A. (2002) DNA Methylation Patterns and Epigenetic Memory. Genes Development, 16, 6-21.
http://dx.doi.org/10.1101/gad.947102
[2] Li, E., Bestor, T.H. and Jaenisch, R. (1992) Targeted Mutation of the DNA Methyltransferase Gene Results in Embryonic Lethality. Cell, 69, 915-926.
http://dx.doi.org/10.1016/0092-8674(92)90611-F
[3] Li, E., Beard, C. and Jaenisch, R. (1993) Role for DNA Methylation in Genomic Imprinting. Nature, 366, 362-365.
http://dx.doi.org/10.1038/366362a0
[4] Okano, M., Bell, D.W., Haber, D.A. and Li, E. (1999) DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for de Novo Methylation and Mammalian Development. Cell, 99, 247-257.
http://dx.doi.org/10.1016/S0092-8674(00)81656-6
[5] Fang, M.Z., Wang, Y.M., Ai, N., Hou, Z., Sun, Y., et al. (2003) Tea Polyphenol (-)-Epigallocatechin-3-Gallate Inhibits DNA Methyltransferase and Reactivates Methylation-Silenced Genes in Cancer Cell Lines. Cancer Research, 63, 7563-7570.
[6] Nguyen, C.T., Gonzales, F.A. and Jones, P.A. (2001) Altered Chromatin Structure Associated with Methylation-Induced Gene Silencing in Cancer Cells: Correlation of Accessibility, Methylation, MeCP2 Binding and Acetylation. Nucleic Acids Research, 29, 4598-4606.
http://dx.doi.org/10.1093/nar/29.22.4598
[7] Rice, J.C., Massey-Brown, K.S. and Futscher, B.W. (1998) Aberrant Methylation of the BRCA1 CpG Island Promoter Is Associated with Decreased BRCA1 mRNA in Sporadic Breast Cancer Cells. Oncogene, 17, 1807-1812.
http://www.stockton-press.co.uk/onc
http://dx.doi.org/10.1038/sj.onc.1202086
[8] Robertson, K.D., Ait-Si-Ali, S., Yokochi, T., Wade, P.A., Jones, P.L. and Wolffe, A.P. (2000) DNMT1 Forms a Complex with Rb, E2F1 and HDAC1 and Represses Transcription from E2F-Responsive Promoters. Nature Genetics, 25, 338-342.
http://dx.doi.org/10.1038/77124
[9] Rountree, M.R., Bachman, K.E. and Baylin, S.B. (2000) DNMT1 binds HDAC2 and a New Co-Repressor, DMAP1, to Form a Complex at Replication Foci. Nature Genetics, 25, 269-277.
http://dx.doi.org/10.1038/77023
[10] Clark, S.J. and Melki, J. (2002) DNA Methylation and Gene Silencing in Cancer: Which Is the Guilty Party? Oncogene, 21, 5380-5387.
http://dx.doi.org/10.1038/sj.onc.1205598
[11] Hurd, P.J., Whitmarsh, A.J., Baldwin, G.S., Kelly, S.M., Waltho, J.P., Price, N.C., et al. (1999) Mechanism-Based Inhibition of C5-Cytosine DNA Methyltransferases by 2-H Pyrimidinone. Journal of Molecular Biology, 286, 389-401.
http://dx.doi.org/10.1006/jmbi.1998.2491
[12] Flotho, C., Claus, R., Batz, C., Schneider, M., Sandrock, I., Ihde, S., Plass, C., Niemeyer, C.M. and Lübbert, M. (2009) The DNA Methyltransferase Inhibitors Azacitidine, Decitabine and Zebularine Exert Differential Effects on Cancer Gene Expression in Acute Myeloid Leukemia Cells. Leukemia, 23, 1019-1028.
http://dx.doi.org/10.1038/leu.2008.397
[13] Jahaniani, F., Ebrahimi, S.A., Rahbar-Roshandel, N. and Mahmoudian, M. (2005) Xanthomicrol Is the Main Cytotoxic Component of Dracocephalum kotschyii and a Potential Anti-Cancer Agent. Photochemistry, 66, 1581-1592.
http://dx.doi.org/10.1016/j.phytochem.2005.04.035
[14] Masuda, T., Iritani, K., Yonemori, S., Oyama, Y. and Takeda, Y. (2001) Isolation and Antioxidant Activity of Galloyl Flavonol Glycosides from the Seashore Plant, Pemphis acidula. Bioscience, Biotechnology, and Biochemistry, 65, 1302-1309.
http://dx.doi.org/10.1271/bbb.65.1302
[15] Huang, H.J., Chen, H.Y., Lee, C.C. and Chen, C.Y. (2014) Computational Design of Apolipoprotein E4 Inhibitors for Alzheimer’s Disease Therapy from Traditional Chinese Medicine. BioMed Research International, 2014, 452-625.
http://dx.doi.org/10.1155/2014/452625
[16] Morris, G.M., Huey, R., Lindstrom, W., Sanner, M.F., Belew, R.K., et al. (2009) Olson, Auto Dock4 and Auto DockTools4: Automated Docking with Selective Receptor Flexibility. Journal of Computational Chemistry, 30, 2785-2791.
http://dx.doi.org/10.1002/jcc.21256

  
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