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

Quaovi Sodji; Vishal Patil; Surendra Jain; James R. Kornacki; Milan Mrksich; Babu L. Tekwani; Adegboyega K. Oyelere

doi:10.1016/j.bmcl.2014.08.060

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

Quaovi Sodji, Vishal Patil, Surendra Jain, James R. Kornacki, Milan Mrksich, Babu L. Tekwani^*, Adegboyega K. Oyelere

^*Corresponding author for this work

Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

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.

Original language	English (US)
Pages (from-to)	4826-4830
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	20
DOIs	https://doi.org/10.1016/j.bmcl.2014.08.060
State	Published - Oct 15 2014

Funding

This work was financially supported by NIH Grant R01CA131217 (A.K.O.) and US Department of Defense CDMPR Grant No. W81XWH-09-2-0093 (B.L.T. & S.K.J.). Q.H.S. is a recipient of the GAANN predoctoral fellowship from the Georgia Tech Center for Drug Design, Development and Delivery and a dissertation fellowship from the Southern Regional Education Board.

Keywords

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

ASJC Scopus subject areas

Drug Discovery
Molecular Medicine
Molecular Biology
Biochemistry
Clinical Biochemistry
Pharmaceutical Science
Organic Chemistry

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10.1016/j.bmcl.2014.08.060

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title = "The antileishmanial activity of isoforms 6- and 8-selective histone deacetylase inhibitors",

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.",

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note = "Funding Information: This work was financially supported by NIH Grant R01CA131217 (A.K.O.) and US Department of Defense CDMPR Grant No. W81XWH-09-2-0093 (B.L.T. & S.K.J.). Q.H.S. is a recipient of the GAANN predoctoral fellowship from the Georgia Tech Center for Drug Design, Development and Delivery and a dissertation fellowship from the Southern Regional Education Board. Publisher Copyright: {\textcopyright} 2014 Elsevier Ltd. All rights reserved.",

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AU - Mrksich, Milan

AU - Tekwani, Babu L.

AU - Oyelere, Adegboyega K.

N1 - Funding Information: This work was financially supported by NIH Grant R01CA131217 (A.K.O.) and US Department of Defense CDMPR Grant No. W81XWH-09-2-0093 (B.L.T. & S.K.J.). Q.H.S. is a recipient of the GAANN predoctoral fellowship from the Georgia Tech Center for Drug Design, Development and Delivery and a dissertation fellowship from the Southern Regional Education Board. Publisher Copyright: © 2014 Elsevier Ltd. All rights reserved.

PY - 2014/10/15

Y1 - 2014/10/15

N2 - 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.

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

Abstract

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Keywords

ASJC Scopus subject areas

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