title: Lysine Deacetylase Inhibitors in Parasites: Past, Present, and Future Perspectives.
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.
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco "Sapienza" Università di Roma , 00185 Rome, Italy.
authors.forename: Gebremedhin S
authors.initials: GS
authors.lastname: Hailu
authors.affiliation: Institute of Pharmacy, Martin-Luther-Universitat Halle-Wittenberg , Halle, Germany.
authors.forename: Dina
authors.initials: D
authors.lastname: Robaa
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco "Sapienza" Università di Roma , 00185 Rome, Italy.|Center for Life Nano Science@Sapienza, Italian Institute of Technology , Viale Regina Elena 291, 00161 Rome, Italy.
authors.forename: Mariantonietta
authors.initials: M
authors.lastname: Forgione
authors.affiliation: Institute of Pharmacy, Martin-Luther-Universitat Halle-Wittenberg , Halle, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sippl
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco "Sapienza" Università di Roma , 00185 Rome, Italy.
authors.forename: Dante
authors.initials: D
authors.lastname: Rotili
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco "Sapienza" Università di Roma , 00185 Rome, Italy.|Istituto Pasteur, Fondazione Cenci-Bolognetti, "Sapienza" Università di Roma , 00185 Rome, Italy.
authors.forename: Antonello
authors.identifier: 0000-0001-9176-2382
authors.initials: A
authors.lastname: Mai
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000494:pharmacology*; D058492:Drug Repositioning; D015801:Helminth Proteins / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000145:classification / Q000378:metabolism; D006801:Humans; D007891:Leishmania / Q000201:enzymology / Q000472:pathogenicity; D010961:Plasmodium / Q000201:enzymology / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000378:metabolism*; D012547:Schistosoma / Q000201:enzymology / Q000472:pathogenicity; D014122:Toxoplasma / Q000201:enzymology / Q000472:pathogenicity; D014345:Trypanosoma / Q000201:enzymology / Q000469:parasitology
chemical_list: D000977:Antiparasitic Agents; D015801:Helminth Proteins; D056572:Histone Deacetylase Inhibitors; D015800:Protozoan Proteins; D006655:Histone Deacetylases