Identification of long chain alkylidenemalonates as novel small molecule modulators of histone acetyltransferases

Gianluca Sbardella; Sabrina Castellano; Caterina Vicidomini; Dante Rotili; Angela Nebbioso; Marco Miceli; Lucia Altucci; Antonello Mai

doi:10.1016/j.bmcl.2008.04.017

Identification of long chain alkylidenemalonates as novel small molecule modulators of histone acetyltransferases

Bioorg Med Chem Lett. 2008 May 1;18(9):2788-92. doi: 10.1016/j.bmcl.2008.04.017. Epub 2008 Apr 11.

Authors

Gianluca Sbardella¹, Sabrina Castellano, Caterina Vicidomini, Dante Rotili, Angela Nebbioso, Marco Miceli, Lucia Altucci, Antonello Mai

Affiliation

¹ Dipartimento di Scienze Farmaceutiche, Università degli Studi di Salerno, Via Ponte Don Melillo, 84084 Fisciano (SA), Italy. gsbardella@unisa.it

PMID: 18434144
DOI: 10.1016/j.bmcl.2008.04.017

Abstract

Pentadecylidenemalonate 1b, a simplified analogue of anacardic acid, was identified as the first mixed activator/inhibitor of histone acetyltransferases (HATs). It potentiates PCAF HAT activity while inhibiting those of p300/CBP and recombinant CBP. The remarkable apoptotic effect together with the ability to selectively acetylate histone versus non-histone substrates appoint 1b as a lead for the development of anticancer drugs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylation
Alkadienes / chemistry*
Antineoplastic Agents* / chemistry
Antineoplastic Agents* / pharmacology
Apoptosis / drug effects*
Apoptosis / physiology
Cell Cycle / drug effects*
Cell Cycle / physiology
Enzyme Inhibitors* / chemistry
Enzyme Inhibitors* / pharmacology
Histone Acetyltransferases / antagonists & inhibitors*
Humans
Malonates / chemistry*
Models, Chemical
U937 Cells
p300-CBP Transcription Factors / antagonists & inhibitors

Substances

Alkadienes
Antineoplastic Agents
Enzyme Inhibitors
Malonates
pentadecylidenemalonate 1b
Histone Acetyltransferases
p300-CBP Transcription Factors
p300-CBP-associated factor