Molecular Diversity

, Volume 15, Issue 2, pp 401–416 | Cite as

Chemical biology of Histone acetyltransferase natural compounds modulators

  • Fabrizio Dal Piaz
  • Antonio Vassallo
  • Osmany Cuesta Rubio
  • Sabrina Castellano
  • Gianluca Sbardella
  • Nunziatina De Tommasi
Comprehensive Review

Abstract

Histone acetyltransferases (HATs) are a class of epigenetic enzymes crucial for chromatin restructuring and transcriptional regulation in eukaryotic cells, thus being a promising target for therapeutic development. Nonetheless, differently from histone deacetylases (HDACs) inhibitors, there is still paucity of small-molecule modulators of HAT activity. After a decline during past decade, natural products and their derivatives could be once again a valuable tool in the lead discovery process and meet such need of Novel Chemical Entities (NCEs). In this review, we will provide a comprehensive summary on the discovery of small-molecule HAT modulators from naturally occurring molecular scaffolds.

Keywords

Histone acetyltransferases Natural compounds Polyisoprenylated benzophenone derivatives Anacardic acid Polyphenols 

Abbreviations

ATF2

Activated transcription factor 2

bZip

Basic-zipper

CBP

CREB-binding protein

CTPB

N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide

DMSO

Dimethyl sulfoxide

EGCG

(−)-Epigallocatechin gallate

ER

Estrogen receptor

FAT

Transcription factor acetyltransferase

GCN5

General control of nitrogen metabolism-5 protein

H2A

Histone H2A

H2B

Histone H2B

H3

Histone H3

H4

Histone H4

HAT

Histone acetyltransferase

HDAC

Histone deacetylase

HeLa

Human uterine cervical carcinoma cells, after the name of Henrietta Lacks, a patient at Johns Hopkins Hospital, Baltimore

HMT

Histone methyltransferase

IG

Isogarcinol

IP-10

Human interferon-inducible protein 10

MCF-7

Michigan Cancer Foundation-7

MIP-2

Macrophage-inflammatory protein-2

MYST

MOZ, YBF2/SAS3, SAS2, TIP60 N-acetyltransferase

MOZ

Monocytic leukaemia zinc-finger protein

NF−κB

Nuclear factor-kappa B

NOS2

Nitric oxide synthase 2

p300/CBP

E1A binding protein p300/CREB-binding protein

p300HD

p300 HAT domain

PBDs

Polyisoprenylated benzophenone derivatives

PBL

Peripheral blood lymphocytes

PC

Prostate cancer

PCAF

p300/CBP-associated factor

SDS-PAGE

Sodium dodecyl sulfate - Polyacrylamide gel electrophoresis

SGR

Sanguinarine

SIRT

Sirtuin

SNL

Solanum nigrum L

SPR

Surface plasmon resonance

SRC1

Steroid receptor coactivator 1

SRC2

Steroid receptor coactivator 2

TAFII250

TBP associated factor II250

TBP

TATA-binding protein

TNF

Tumor necrosis factor

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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Fabrizio Dal Piaz
    • 1
  • Antonio Vassallo
    • 2
  • Osmany Cuesta Rubio
    • 3
  • Sabrina Castellano
    • 1
  • Gianluca Sbardella
    • 1
  • Nunziatina De Tommasi
    • 1
  1. 1.Dipartimento di Scienze FarmaceuticheUniversità di SalernoFisciano (SA)Italy
  2. 2.Dipartimento di ChimicaUniversità degli Studi della BasilicataPotenza (PZ)Italy
  3. 3.Universidad de La HabanaHavanaCuba

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