A series of potent and selective, triazolylphenyl-based histone deacetylases inhibitors with activity against pancreatic cancer cells and Plasmodium falciparum

Yufeng Chen, Miriam Lopez-Sanchez, Doris N. Savoy, Daniel D Billadeau, Geoffrey S. Dow, Alan P. Kozikowski

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

The discovery of the rules governing the inhibition of the various HDAC isoforms is likely to be key to identifying improved therapeutics that act as epigenetic modulators of gene transcription. Herein we present results on the modification of the CAP region of a set of triazolylphenyl-based HDACIs, and show that the nature of substitution on the phenyl ring plays a role in their selectivity for HDAC1 versus HDAC6, with low to moderate selectivity (2-51-fold) being achieved. In light of the valuable selectivity and potency that were identified for the triazolylphenyl ligand 6b in the inhibition of HDAC6 (IC 50 = 1.9 nM), this compound represents a valuable research tool and a candidate for further chemical modifications. Lastly, these new HDACIs were studied for both their anticancer and antimalarial activity, which serve to validate the superior activity of the HDACI 10c.

Original languageEnglish (US)
Pages (from-to)3437-3448
Number of pages12
JournalJournal of Medicinal Chemistry
Volume51
Issue number12
DOIs
StatePublished - Jun 26 2008

Fingerprint

Histone Deacetylases
Chemical modification
Antimalarials
Transcription
Plasmodium falciparum
Pancreatic Neoplasms
Epigenomics
Modulators
Protein Isoforms
Substitution reactions
Genes
Cells
Ligands
Research
Therapeutics

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

A series of potent and selective, triazolylphenyl-based histone deacetylases inhibitors with activity against pancreatic cancer cells and Plasmodium falciparum. / Chen, Yufeng; Lopez-Sanchez, Miriam; Savoy, Doris N.; Billadeau, Daniel D; Dow, Geoffrey S.; Kozikowski, Alan P.

In: Journal of Medicinal Chemistry, Vol. 51, No. 12, 26.06.2008, p. 3437-3448.

Research output: Contribution to journalArticle

Chen, Yufeng ; Lopez-Sanchez, Miriam ; Savoy, Doris N. ; Billadeau, Daniel D ; Dow, Geoffrey S. ; Kozikowski, Alan P. / A series of potent and selective, triazolylphenyl-based histone deacetylases inhibitors with activity against pancreatic cancer cells and Plasmodium falciparum. In: Journal of Medicinal Chemistry. 2008 ; Vol. 51, No. 12. pp. 3437-3448.
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