Recent advancement of HDAC inhibitors against breast cancer

Syed Abdulla Mehmood1, Kantrol Kumar Sahu2, Sounok Sengupta3

  • 1Department of Pharmacology, School of Pharmaceutical Education & Research, Jamia Humdard University, New Delhi, India.

Insights

Histone deacetylase inhibitors (HDACis) show promise for triple-negative breast cancer (TNBC) treatment. Belinostat demonstrated the best binding affinity to histone deacetylase protein in molecular docking studies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Triple-negative breast cancer (TNBC) lacks effective therapies, necessitating novel treatment strategies.
  • Histone deacetylases (HDACs) regulate cellular processes crucial for cancer development.
  • Histone deacetylase inhibitors (HDACis) are being explored for their therapeutic potential in TNBC.

Purpose of the Study:

  • To discuss pharmacophoric models and structural alterations of HDACis for potent TNBC inhibition.
  • To investigate the therapeutic potential of HDAC inhibitors against TNBC.
  • To perform molecular docking and dynamic simulation of HDAC inhibitors.

Main Methods:

  • Analysis of HDACis pharmacophoric models and structural modifications.
  • Molecular docking study of four HDAC inhibitors against histone deacetylase protein.
  • Molecular dynamic simulation of the best-docked compound.

Main Results:

  • Belinostat exhibited the highest binding affinity (-8.7 kJ/mol) to histone deacetylase protein.
  • Belinostat formed five conventional hydrogen bonds with key amino acid residues (Gly 841, His 669, His 670, Pro 809, His 709).
  • Structural insights into HDAC inhibition provide a basis for developing novel TNBC therapeutics.

Conclusions:

  • HDAC inhibitors, particularly belinostat, hold significant potential for TNBC treatment.
  • Pharmacophore modeling and molecular simulations are valuable tools for designing effective HDACis.
  • Further development of selective and polypharmacological HDAC strategies is warranted for TNBC.

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