In silico studies on modified hydroxamic acid and valporic acid as potential inhibitors for HDAC2

Authors

  • Naresh Kandakatla Department of Chemistry, Sathayabama University, Jeppiaar Nagar, Chennai
  • Shikha Rathaur Department of Chemistry, Sathayabama University, Jeppiaar Nagar, Chennai
  • Smruti Sandhya Sahoo Department of Bioinformatics, Sathayabama University, Jeppiaar Nagar, Chennai
  • Geetha Ramakrishnan Department of Chemistry, Sathayabama University, Jeppiaar Nagar, Chennai

DOI:

https://doi.org/10.3329/bjp.v8i3.15433

Keywords:

HDAC2, Hydroxamic acid, Molecular docking, SAHA, Valporic acid

Abstract

Histone deacetylases2, Class 1 HDAC family are emerged as an important therapeutic target for the treatment of various cancers. HDAC2 inhibitors are potent anti-cancer agents. Two inhibitors of HDAC2 are hydroxamic acid and valporic acid which are potent inducers of growth arrest, differentiation, and/or apoptotic cell death. Total 34 ligands optimized using triazole group substitution for the target protein Histone deacetylase2 on the basis of SAHA and valporic acid. All the ligands are docked with the target protein and results are compared with test compound SAHA. Eight ligands showed better binding affinity towards HDAC2.The binding affinity, free energy and drug scan screening of the above eight ligands have shown that P2, P6 and V6 molecules are best suitable to inhibit HDAC2.

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References

Alonso H, Bliznyuk AA, Gready JE. Combining docking and molecular dynamic simulation in drug design. Med Res Rev. 2006; 26: 531-68.

Bhakat S. SAR and pharmacophore based designing of some antimalarial and antiretroviral agents: An internet based drug design approach. Der Pharma Chemica. 2012; 4: 1247-63.

Bieliauskas AV. Pflum MKH. Isoform-selective histone deacetylase inhibitors. Chem Soc Rev. 2008; 37: 1402-13.

Copeland RA. Evaluation of enzyme inhibitors in drug discovery: A guide for medicinal chemists and pharmacologists. New Jersey, Wiley Interscience, 2005.

Lindemann RK, Johnstone RW. Histone deacetylase inhibitors: promising candidates for chemotherapeutic drugs. Gene Ther Mol Biol. 2004; 8: 61-74.

Mai A, Massa S, Ragno R, Esposito M, Sbardella G, Nocca G, Scatena R, Jesacher F, Loidl P, Brosch G. Binding mode analysis of 3-(4-benzoyl-1-methyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamide: A new synthetic histone deacetylase inhibitor inducing histone hyperacetylation, growth inhibition, and terminal cell differentiation. J Med Chem. 2002; 40: 1-13.

Marks PA. Discovery and development of SAHA as an anticancer agent. Oncogene 2007; 26: 1351-56.

Monneret C. Histone deacetylase inhibitors. Eur J Med Chem. 2005; 40: 1-13.

Prince HM, Bishton M. Panobinostat (LBH589): A novel pan-deacetylase inhibitor with activity in T cell lymphoma. Hemat Meet Rep. 2009; 3: 33-38.

Roffey J. Bioisosteres in medicinal chemistry. Maybridge Med Chem. 1997; 1: 23-44.

Walkinshaw DR, Yang XJ. Histone deacetylase inhibitors as novel anticancer therapeutics. Curr Oncol. 2008; 15: 237-43.

Venkatachalam CM, Jiang X, Oldfield T, Waldman M. LigandFit: A novel method for the shape-directed rapid docking of ligands to protein active sites. J Mol Graph Mod. 2003; 21: 289.

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Published

2013-07-18

How to Cite

Kandakatla, Naresh, et al. “In Silico Studies on Modified Hydroxamic Acid and Valporic Acid As Potential Inhibitors for HDAC2”. Bangladesh Journal of Pharmacology, vol. 8, no. 3, July 2013, pp. 328-35, doi:10.3329/bjp.v8i3.15433.

Issue

Vol. 8 No. 3 (2013)

Section

Research Articles

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