The antileishmanial activity of isoforms 6- and 8-selective histone deacetylase inhibitors

Bioorg Med Chem Lett. 2014 Oct 15;24(20):4826-30. doi: 10.1016/j.bmcl.2014.08.060.

Quaovi Sodji ¹, Vishal Patil ¹, Surendra Jain ², James R Kornacki ³, Milan Mrksich ³, Babu L Tekwani ⁴, Adegboyega K Oyelere ⁵

Affiliations

1 School of Chemistry and Biochemistry, Parker H. Petit for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA.
2 National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS 38677-1848, USA.
3 Department of Chemistry and Biomedical Engineering, Northwestern University, 2145 Sheridan Rd, Evanston, IL 60208-3113, USA.
4 National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS 38677-1848, USA. Electronic address: btekwani@olemiss.edu.
5 School of Chemistry and Biochemistry, Parker H. Petit for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA. Electronic address: aoyelere@gatech.edu.

PMID: 25240614 DOI: 10.1016/j.bmcl.2014.08.060

Abstract

Histone deacetylase inhibitors (HDACi) pleiotropy is largely due to their nonselective inhibition of various cellular HDAC isoforms. Connecting inhibition of a specific isoform to biological responses and/or phenotypes is essential toward deconvoluting HDACi pleiotropy. The contribution of classes I and II HDACs to the antileishmanial activity of HDACi was investigated using the amastigote and promastigote forms of Leishmania donovani. We observed that the antileishmanial activities of HDACi are largely due to the inhibition of HDAC6-like activity. This observation could facilitate the development of HDACi as antileishmanial agents.

Keywords

3-Hydroxypyridin-2-thione; Histone deacetylase inhibitors; Leishmania donovani; Trichostatin A; Tubastatin A.

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