Antimalarial and antileishmanial activities of histone deacetylase inhibitors with triazole-linked cap group.

Bioorganic & Medicinal Chemistry
Vishal PatilAdegboyega K Oyelere

Abstract

Histone deacetylase inhibitors (HDACi) are endowed with plethora of biological functions including anti-proliferative, anti-inflammatory, anti-parasitic, and cognition-enhancing activities. Parsing the structure-activity relationship (SAR) for each disease condition is vital for long-term therapeutic applications of HDACi. We report in the present study specific cap group substitution patterns and spacer-group chain lengths that enhance the antimalarial and antileishmanial activity of aryltriazolylhydroxamates-based HDACi. We identified many compounds that are several folds selectively cytotoxic to the plasmodium parasites compared to standard HDACi. Also, a few of these compounds have antileishmanial activity that rivals that of miltefosine, the only currently available oral agent against visceral leishmaniasis. The anti-parasite properties of several of these compounds tracked well with their anti-HDAC activities. The results presented here provide further evidence on the suitability of HDAC inhibition as a viable therapeutic option to curb infections caused by apicomplexan protozoans and trypanosomatids.

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Citations

Jul 31, 2010·Journal of Medicinal Chemistry·Sandra C MwakwariAdegboyega K Oyelere
Apr 4, 2013·Journal of Medicinal Chemistry·Vishal PatilAdegboyega K Oyelere
Jun 22, 2013·Journal of Medicinal Chemistry·Berkley E GryderAdegboyega K Oyelere
Nov 30, 2011·Immunology and Cell Biology·Katherine T AndrewsMalcolm K Jones
Mar 16, 2012·Future Medicinal Chemistry·Berkley E GryderAdegboyega K Oyelere
Jul 23, 2015·International Journal for Parasitology. Drugs and Drug Resistance·Jessica A EngelKatherine T Andrews
Nov 26, 2015·Journal of Molecular Graphics & Modelling·Jelena MelesinaWolfgang Sippl
May 8, 2014·Chemical Biology & Drug Design·Núbia BoechatAntoniana U Krettli
Jun 15, 2016·Journal of Natural Medicines·Muna Ali Abdalla
Feb 28, 2017·Journal of Medicinal Chemistry·Gebremedhin S HailuAntonello Mai
Jan 28, 2017·Bioorganic Chemistry·Divya DheerRavi Shankar
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Jan 15, 2019·Dalton Transactions : an International Journal of Inorganic Chemistry·Abdallah G MahmoudArmando J L Pombeiro
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Sep 26, 2014·Chemical Reviews·Hidayat HussainSimon Gibbons
May 12, 2020·Journal of Medicinal Chemistry·Victoriano Corpas-LópezJosé A Gómez-Vidal

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