Characterizing binding intensity and energetic features of histone deacetylase inhibitor pracinostat towards class I HDAC isozymes through futuristic drug designing strategy

Abstract

Pracinostat, an emerging hydroxamate histone deacetylase (HDAC) inhibitor has shown better efficacy than approved inhibitor suberoylanilide hydroxamic acid (SAHA). Apart from haematological malignancies, this inhibitor has shown promising results in preclinical models of solid tumours. Being pan-inhibitor pracinostat targets various classical HDACs and has demonstrated antiproliferative properties in a series of cancer cell lines. Currently, no energetic and structural studies are available about the pracinostat against four HDAC isozymes of Class I. Taking this into account, the current study involved flexible molecular docking for gaining insights regarding pracinostat-HDAC isozyme interactions, molecular mechanics generalized born surface area (MM-GBSA) for estimating binding affinity of this inhibitor towards these isozymes and energetically optimized pharmacophores (e-Pharmacophores) technique for delineating the critical e-pharmacophoric features of pracinostat in its least energy state in the binding pocket of these HDACs. The outcome from this study will help in further optimization of pracinostat towards better therapeutic and the e-Pharmacophores generated will serve as queries in e-Pharamcophores guided virtual screening.

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Acknowledgements

Ganai SA acknowledges monetary support from Science and Engineering Research Board. The author used the power facility of SDAU palanpur for writing this manuscript.

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Correspondence to Shabir Ahmad Ganai.

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Ganai, S.A. Characterizing binding intensity and energetic features of histone deacetylase inhibitor pracinostat towards class I HDAC isozymes through futuristic drug designing strategy. In Silico Pharmacol. 9, 18 (2021). https://doi.org/10.1007/s40203-021-00077-y

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Keywords

  • Pracinostat
  • HDAC1-3
  • HDAC8
  • XP-molecular docking
  • CB-Dock
  • MM-GBSA
  • e-Pharmacophores method