Journal of Integrative Natural Science (통합자연과학논문집)

The Basic Science Institute Chosun University (조선대학교 기초과학연구원)
권호 표지
DOI QR코드

DOI QR Code

Virtual Screening, Docking and DFT Study of PRMT5

  • Subathra, S (Department of Genetics, Chettinad Health and Research Institute)
  • Received : 2022.11.25
  • Accepted : 2022.12.20
  • Published : 2022.12.30
Download PDF
⟨ Previous Next ⟩

Abstract

Protein Arginine Methyltransferase 5 (PRMT5), a significant member of the PRMT family, is a promising anticancer target. In this study, novel small compounds that act against the PRMT5 target are found by combining virtual screening with ChEMBL database medicines and Density Functional Theory. The ChEMBL database compounds were screened to retrieve the hit molecules, which further subjected for DFT analysis. Finally we have evaluated that ChEMBL- approved drugs such as Lifitegrast, Abiraterone acetate and Solifenacin may be potential inhibitors for PRMT5.

Keywords

References

  1. Yang Z, Xiao T, Li Z, Zhang J, Chen S. Novel Chemicals Derived from Tadalafil Exhibit PRMT5 Inhibition and Promising Activities against Breast Cancer. Int J Mol Sci 2022;23(9).
  2. Kim H, Ronai ZA. PRMT5 function and targeting in cancer. Cell Stress 2020;4(8):199-215.
  3. Asberry AM, Cai X, Deng X, Santiago U, Liu S, Sims HS, et al. Discovery and Biological Characterization of PRMT5: MEP50 Protein-Protein Interaction Inhibitors. J Med Chem 2022;65(20):13793-812. https://doi.org/10.1021/acs.jmedchem.2c01000
  4. Yan Y, Zhao P, Wang Z, Liu Z, Wang Z, Zhang J, et al. PRMT5 regulates colorectal cancer cell growth and EMT via EGFR/Akt/GSK3β signaling cascades. Aging (Albany NY) 2021;13(3):4468-81.
  5. Zhang Q, Zhang L, Jin J, FanY, Wang X, Hu H, et al. Identification of PRMT5 inhibitors with novel scaffold structures through virtual screening and biological evaluations. J Mol Model [Internet] 2022;28(7):184. Available from: https://doi.org/10.1007/s00894-022-05125-8
  6. Antonysamy S, Bonday Z, Campbell RM, Doyle B, Druzina Z, Gheyi T, et al. Crystal structure of the human PRMT5:MEP50 complex. Proc Natl Acad Sci U S A 2012;109(44):17960-5. https://doi.org/10.1073/pnas.1209814109
  7. Tao H, Yan X, Zhu K, Zhang H. Discovery of Novel PRMT5 Inhibitors by Virtual Screening and Biological Evaluations. Chem Pharm Bull (Tokyo) 2019;67(4):382-8. https://doi.org/10.1248/cpb.c18-00980
  8. Kulkarni SA, Nagarajan SK, Ramesh V, Palaniyandi V, Selvam SP, Madhavan T. Computational evaluation of major components from plant essential oils as potent inhibitors of SARS-CoV-2 spike protein. J Mol Struct 2020;1221:128823.
  9. Bathula R, Lanka G, Chakravarty M, Somadi G, Sivan SK, Jain A, et al. Structural insight into PRMT5 inhibitors through amalgamating pharmacophore-based virtual screening, ADME toxicity, and binding energy studies to identify new inhibitors by molecular docking. Struct Chem 2022;33(4):1223-39. https://doi.org/10.1007/s11224-022-01918-y
  10. Prabhu L, Martin M, Chen L, Demir O, Jin J, Huang X, et al. Inhibition of PRMT5 by market drugs as a novel cancer therapeutic avenue. Genes Dis [Internet] 2022;Available from: https://www.sciencedirect.com/science/article/pii/S2352304222000939