Abstract:
:Histone deacetylase (HDAC) enzymes work together with histone acetyltransferases (HATs) to reversibly acetylate both histone and non-histone proteins. As a result, these enzymes are involved in regulating chromatin structure and gene expression as well as other important cellular processes. HDACs are validated drug targets for some types of cancer, with four HDAC inhibitors clinically approved. However, they are also showing promise as novel drug targets for other indications, including malaria and other parasitic diseases. In this study the in vitro activity of four anti-cancer HDAC inhibitors was examined against parasites that cause malaria and trypanosomiasis. Three of these inhibitors, suberoylanilide hydroxamic acid (SAHA; vorinostat(®)), romidepsin (Istodax(®)) and belinostat (Beleodaq(®)), are clinically approved for the treatment of T-cell lymphoma, while the fourth, panobinostat, has recently been approved for combination therapy use in certain patients with multiple myeloma. All HDAC inhibitors were found to inhibit the growth of asexual-stage Plasmodium falciparum malaria parasites in the nanomolar range (IC50 10-200 nM), while only romidepsin was active at sub-μM concentrations against bloodstream form Trypanosoma brucei brucei parasites (IC50 35 nM). The compounds were found to have some selectivity for malaria parasites compared with mammalian cells, but were not selective for trypanosome parasites versus mammalian cells. All compounds caused hyperacetylation of histone and non-histone proteins in P. falciparum asexual stage parasites and inhibited deacetylase activity in P. falciparum nuclear extracts in addition to recombinant PfHDAC1 activity. P. falciparum histone hyperacetylation data indicate that HDAC inhibitors may differentially affect the acetylation profiles of histone H3 and H4.
journal_name
Int J Parasitol Drugs Drug Resistauthors
Engel JA,Jones AJ,Avery VM,Sumanadasa SD,Ng SS,Fairlie DP,Skinner-Adams T,Andrews KTdoi
10.1016/j.ijpddr.2015.05.004subject
Has Abstractpub_date
2015-06-20 00:00:00pages
117-26issue
3issn
2211-3207pii
S2211-3207(15)00012-3journal_volume
5pub_type
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journal_title:International journal for parasitology. Drugs and drug resistance
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journal_title:International journal for parasitology. Drugs and drug resistance
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journal_title:International journal for parasitology. Drugs and drug resistance
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journal_title:International journal for parasitology. Drugs and drug resistance
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journal_title:International journal for parasitology. Drugs and drug resistance
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journal_title:International journal for parasitology. Drugs and drug resistance
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journal_title:International journal for parasitology. Drugs and drug resistance
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journal_title:International journal for parasitology. Drugs and drug resistance
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journal_title:International journal for parasitology. Drugs and drug resistance
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journal_title:International journal for parasitology. Drugs and drug resistance
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journal_title:International journal for parasitology. Drugs and drug resistance
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journal_title:International journal for parasitology. Drugs and drug resistance
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doi:10.1016/j.ijpddr.2020.10.004
更新日期:2020-12-01 00:00:00
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journal_title:International journal for parasitology. Drugs and drug resistance
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doi:10.1016/j.ijpddr.2020.11.004
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journal_title:International journal for parasitology. Drugs and drug resistance
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2017.10.002
更新日期:2017-12-01 00:00:00
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2019.01.003
更新日期:2019-04-01 00:00:00
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2013.04.002
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2012.02.004
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章,评审
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2014.10.002
更新日期:2014-10-25 00:00:00
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2019.08.003
更新日期:2019-08-01 00:00:00
abstract::Toxicity and poor adherence to treatment that favors the generation of resistance in the Leishmania parasites highlight the need to develop better alternatives. Here, we evaluated the in vitro effectiveness of hydrazone derived from chromanes 2-(2,3-dihydro-4H-1-benzothiopyran-4-ylidene) hydrazide (TC1) and 2-(2,3-dih...
journal_title:International journal for parasitology. Drugs and drug resistance
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abstract:OBJECTIVES:This study evaluated the implications of clinically acquired miltefosine resistance (MIL-R) by assessing virulence in mice and sand flies to reveal the potential of MIL-R strains to circulate. METHODS:Experimental infections with the MIL-R clinical Leishmania infantum isolate MHOM/FR/2005/LEM5159, having a ...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2020.04.004
更新日期:2020-08-01 00:00:00
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journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2017.03.005
更新日期:2017-08-01 00:00:00
abstract::Anthelmintic resistance (AR) to Fasciola hepatica is emerging worldwide. Recently, AR to the adulticide compound albendazole (ABZ) was shown in Argentina and Spain. In Sweden, ABZ treatment failure against F. hepatica was first reported in sheep in 2012. The present study tested the efficacy of ABZ and triclabendazole...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2016.06.004
更新日期:2016-12-01 00:00:00
abstract::The need for new antimalarials is persistent due to the emergence of drug resistant parasites. Here we aim to identify new drug targets in Plasmodium falciparum by phylogenomics among the Plasmodium spp. and comparative genomics to Homo sapiens. The proposed target discovery pipeline is largely independent of experime...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2012.07.002
更新日期:2012-07-17 00:00:00
abstract::The control of parasitic nematodes impacting animal health relies on the use of broad spectrum anthelmintics. However, intensive use of these drugs has led to the selection of resistant parasites in livestock industry. In that respect, there is currently an urgent need for novel compounds able to control resistant par...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2018.11.003
更新日期:2018-12-01 00:00:00
abstract::Schistosomiasis is a neglected tropical disease caused by blood-dwelling flukes of the genus Schistosoma. While the disease may affect as many as 249 million people, treatment largely relies on a single drug, praziquantel. The near exclusive use of this drug for such a prevalent disease has led to concerns regarding t...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2014.09.006
更新日期:2014-09-26 00:00:00
abstract::Macrocyclic lactone (ML) anthelmintics are the most important class of anthelmintics because of our high dependence on them for the control of nematode parasites and some ectoparasites in livestock, companion animals and in humans. However, resistance to MLs is of increasing concern. Resistance is commonplace througho...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章,评审
doi:10.1016/j.ijpddr.2019.06.002
更新日期:2019-08-01 00:00:00
abstract::Knockdown-resistance (kdr) against pyrethroids in bed bugs (Cimex lectularis) is associated with the presence of several point mutations in the voltage-sensitive sodium channel α-subunit gene and/or an increased metabolic detoxification by cytochrome P450 monooxygenases (CYPs). In the present study, pyrosequencing ass...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2020.11.003
更新日期:2020-12-01 00:00:00