Current therapies for human parasite infections rely on a few drugs, most of which have severe side effects, and their helpfulness is being seriously compromised by the drug resistance problem. Globally, this is pushing discovery research of antiparasitic drugs toward new agents endowed with new mechanisms of action. By using a "drug repurposing" strategy, histone deacetylase inhibitors (HDACi), which are presently clinically approved for cancer use, are now under investigation for various parasite infections. Because parasitic Zn2+- and NAD+-dependent HDACs play crucial roles in the modulation of parasite gene expression and many of them are pro-survival for several parasites under various conditions, they are now emerging as novel potential antiparasitic targets. This Perspective summarizes the state of knowledge of HDACi (both class I/II HDACi and sirtuin inhibitors) targeted to the main human parasitic diseases (schistosomiasis, malaria, trypanosomiasis, leishmaniasis, and toxoplasmosis) and provides visions into the main issues that challenge their development as antiparasitic agents.

Lysine deacetylase inhibitors in parasites: past, present, and future perspectives / Hailu, Gs; Robaa, D; Forgione, M; Sippl, W; Rotili, D; Mai, A.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - ELETTRONICO. - 60:12(2017), pp. 4780-4804. [10.1021/acs.jmedchem.6b01595]

Lysine deacetylase inhibitors in parasites: past, present, and future perspectives.

Hailu GS;Rotili D
;
Mai A.
2017

Abstract

Current therapies for human parasite infections rely on a few drugs, most of which have severe side effects, and their helpfulness is being seriously compromised by the drug resistance problem. Globally, this is pushing discovery research of antiparasitic drugs toward new agents endowed with new mechanisms of action. By using a "drug repurposing" strategy, histone deacetylase inhibitors (HDACi), which are presently clinically approved for cancer use, are now under investigation for various parasite infections. Because parasitic Zn2+- and NAD+-dependent HDACs play crucial roles in the modulation of parasite gene expression and many of them are pro-survival for several parasites under various conditions, they are now emerging as novel potential antiparasitic targets. This Perspective summarizes the state of knowledge of HDACi (both class I/II HDACi and sirtuin inhibitors) targeted to the main human parasitic diseases (schistosomiasis, malaria, trypanosomiasis, leishmaniasis, and toxoplasmosis) and provides visions into the main issues that challenge their development as antiparasitic agents.
2017
plasmodium-falciparum sir2; spectrum antiprotozoal agents; human african trypanosomiasis; neglected tropical diseases; human histone deacetylase; activity in-vitro; schistosoma-mansoni; antileishmanial activity; antimalarial activity; toxoplasma-gondii
01 Pubblicazione su rivista::01a Articolo in rivista
Lysine deacetylase inhibitors in parasites: past, present, and future perspectives / Hailu, Gs; Robaa, D; Forgione, M; Sippl, W; Rotili, D; Mai, A.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - ELETTRONICO. - 60:12(2017), pp. 4780-4804. [10.1021/acs.jmedchem.6b01595]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1027812
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