IAI SPECIAL EDITION: Molecular docking study of vemurafenib derivatives on melanoma inhibitory activity (MIA) as anti-melanoma

Authors

  • Fauzan Zein Muttaqin Bhakti Kencana University, Indonesia
  • Anita Pramudya Ratna Sari Bhakti Kencana University, Indonesia
  • Fransiska Kurniawan Bandung Institute of Technology, Indonesia

DOI:

https://doi.org/10.46542/pe.2022.222.284288

Keywords:

Blind-docking, Melanoma, Melanoma Inhibitory Activity (MIA, Vemurafenib

Abstract

Background: Melanoma is one of the cancers with high mortality rates in Indonesia. The newest potential anti-melanoma target is the Melanoma Inhibitory Activity (MIA/5IXB) macromolecule, but the location of the binding pocket interaction is unknown. Vemurafenib is known to be active in vivo as against melanoma. Thus, it can be used as a lead compound. This study aimed to examine the location of the binding pocket and the interactions that occur between macromolecules and the test compounds.    

Methods: It was carried out using the blind docking method between vemurafenib and an MIA macromolecule.   

Results: The results showed that the best molecular docking was obtained in the distribution of the grid box area in the third area with a ∆G value of -7.80 kcal/mol. Docking validation results showed the value of ∆G 11.06 kcal/mol with an average value of RMSD 1.788 Å, and the amino acid residues that played a role in the interaction were MET31, TYR30, and PRO33. Targeted docking to the binding pocket results on 45 test compounds showed that the most potent compound was Compound-17 with a ∆G value of 11.31 kcal/mol with hydrophobic bond interactions on amino acid residues TYR30. This hydrophobic bond is responsible for the MIA mechanism as an inhibitor of melanoma cell metastasis in the body. It can be concluded that the binding pocket of the MIA(5IXB) macromolecule with the vemurafenib compound is at the amino acid residues MET31, TYR30, and PRO33 with the interaction of hydrogen bonds and hydrophobic bonds. Also, it was observed that T.C-17 is the most potential anti-melanoma test compound.

Author Biographies

Fauzan Zein Muttaqin , Bhakti Kencana University, Indonesia

Faculty of Pharmacy

Anita Pramudya Ratna Sari, Bhakti Kencana University, Indonesia

Faculty of Pharmacy

Fransiska Kurniawan, Bandung Institute of Technology, Indonesia

School of Pharmacy

References

Du, J., Lu, X., Long, Z., Zhang, Z., Zhu, X., Yang, Y., & Xu, J. (2013). n Vitro and in Vivo Anticancer Activity of Aconitine on Melanoma Cell Line B16. International Journal of Molecular Sciences, 18(1), 757–767. https://doi.org/10.3390/molecules18010757

Hernandez-Davies, J. E., Tran, T. Q., Reid, M. A., Rosales, K. R., Lowman, X. H., Pan, M., Moriceau, G., Yang, Y., Wu, J., Lo, R. S., & Kong, M. (2015). Vemurafenib resistance reprograms melanoma cells towards glutamine dependence. Journal of Translational Medicine, 13(1). https://doi.org/10.1186/s12967-015-0581-2

Hevener, K. E., Zhao, W., Ball, D. M., Babaoglu, K., Qi, J., White, S. W., & Lee, R. E. (2009). Validation of molecular docking programs for virtual screening against dihydropteroate synthase. Journal of Chemical Information and Modeling, 49(2), 444–460. https://doi.org/10.1021/ci800293n

Khedekar, P., Kerzare, D. R., Khedekar, P. B., & Kerzarea, D. R. (2016). Indole Derivatives acting on Central Nervous System-Review.Journal of Pharmaceutical sciences and bioscientific research. 2016, 6(1), 144–156. www.jpsbr.org

Madonna, G., Ullman, C. D., Gentilcore, G., Palmieri, G., & Ascierto, P. A. (2012). NF-κB as potential target in the treatment of melanoma. In Journal of Translational Medicine (Vol. 10, Issue 1). https://doi.org/10.1186/1479-5876-10-53

Perera, E., Gnaneswaran, N., Jennens, R., & Sinclair, R. (2014). Malignant melanoma. In Healthcare (Switzerland) (Vol. 2, Issue 1, pp. 1–19). MDPI. https://doi.org/10.3390/healthcare2010001

Schmidt, J., Riechers, A., Stoll, R., Amann, T., Fink, F., Spruss, T., Gronwald, W., König, B., Hellerbrand, C., & Bosserhoff, A. K. (2012). Targeting melanoma metastasis and immunosuppression with a new mode of melanoma inhibitory activity (MIA) protein inhibition.Public Library of Science, 7(5). https://doi.org/10.1371/journal.pone.0037941

Varma, A. K., Patil, R., Das, S., Stanley, A., Yadav, L., & Sudhakar, A. (2010). Optimized hydrophobic interactions and hydrogen bonding at the target-ligand interface leads the pathways of Drug-Designing.Public Library of Science, 5(8). https://doi.org/10.1371/journal.pone.0012029

Yip, K. T., Zhong, X. Y., Seibel, N., Pütz, S., Autzen, J., Gasper, R., Hofmann, E., Scherkenbeck, J., & Stoll, R. (2016). Small Molecules Antagonise the MIA-Fibronectin Interaction in Malignant Melanoma. Scientific Reports, 6. https://doi.org/10.1038/srep25119

Downloads

Published

2022-03-31

How to Cite

Muttaqin , F. Z. ., Sari, A. P. R., & Kurniawan, F. (2022). IAI SPECIAL EDITION: Molecular docking study of vemurafenib derivatives on melanoma inhibitory activity (MIA) as anti-melanoma. Pharmacy Education, 22(2), p. 284–288. https://doi.org/10.46542/pe.2022.222.284288

Issue

Section

Special Edition