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The antileishmanial activity of isoforms 6- and 8-selective histone deacetylase inhibitors
Institution: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;1. School of Chemistry and Chemical Engineering, Institute of Pharmaceutical Engineering, Southeast University, 87 Dingjiaqiao, Nanjing, Jiangsu 210096, PR China;2. Department of Medicinal Chemistry and The Institute for Therapeutics Discovery and Development, University of Minnesota, 717 Delaware Street SE, Minneapolis, MN 55414, USA;3. Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA;4. School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, PR China;1. Université de Lyon, Laboratoire Chimie Organique 2-Glycochimie, ICBMS, UMR-5246, CNRS-Université Claude Bernard Lyon 1, Bât. 308 CPE Lyon, 43 Bd du 11 Novembre 1918, F-69622 Villeurbanne, France;2. University of Milano-Bicocca, Department of Health Sciences, Via Cadore 48, 20052 Monza, Italy;3. University of Geneva, School of Pharmaceutical Sciences, Quai Ernest-Ansermet 30, 1211 Geneva 4, Switzerland;1. Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati, India;2. Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati, India;1. Instituto de Química Médica (IQM-CSIC), E-28006 Madrid, Spain;2. Área de Farmacología, Departamento de Ciencias Biomédicas, Unidad Asociada al IQM-CSIC, Universidad de Alcalá, E-28805 Alcalá de Henares, Madrid, Spain;3. Departamento de Biología de Sistemas, Universidad de Alcalá, E-28805 Alcalá de Henares, Madrid, Spain;1. Comp. Physics Lab, Institute of Technology, Vietnam National University – HochiMinh City, 268 Ly Thuong Kiet Street, District 10, HochiMinh City, Viet Nam;2. Dept. of Physics, School of Natural Sciences, Can Tho University, Can Tho City, Viet Nam;3. Department of Physics, Tokyo Denki University, Hatoyama Hikigun, Saitama 350-0394, Japan;1. Key Laboratory of Luminescence and Optical Information, Ministry of Education, Institute of Optoelectronic Technology, Beijing Jiaotong University, Beijing 100044, PR China;2. Key Laboratory of Photochemical Conversion and Optoelectronic Materials, TIPC, CAS, PR China
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:Histone deacetylase inhibitors  Trichostatin A  Tubastatin A  3-Hydroxypyridin-2-thione
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