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© Christine Schmitt, Sophie Goyard, Jean-Marc Panaud
Trypanosoma cruzi - trypomastigote form. Trypanosoma cruzi is the etiological agent of Chagas disease.
Publication : ACS infectious diseases

Effects of Structurally Different HDAC Inhibitors against Trypanosoma cruzi, Leishmania, and Schistosoma mansoni.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in ACS infectious diseases - 22 Jun 2022

Di Bello E, Noce B, Fioravanti R, Zwergel C, Valente S, Rotili D, Fianco G, Trisciuoglio D, Mourão MM, Sales P, Lamotte S, Prina E, Späth GF, Häberli C, Keiser J, Mai A,

Link to Pubmed [PMID] – 35732073

Link to DOI – 10.1021/acsinfecdis.2c00232

ACS Infect Dis 2022 Jun; ():

Neglected tropical diseases (NTDs), including trypanosomiasis, leishmaniasis, and schistosomiasis, result in a significant burden in terms of morbidity and mortality worldwide every year. Current antiparasitic drugs suffer from several limitations such as toxicity, no efficacy toward all of the forms of the parasites’ life cycle, and/or induction of resistance. Histone-modifying enzymes play a crucial role in parasite growth and survival; thus, the use of epigenetic drugs has been suggested as a strategy for the treatment of NTDs. We tested structurally different HDACi 1-9, chosen from our in-house library or newly synthesized, against Trypanosoma cruzi, Leishmania spp, and Schistosoma mansoni. Among them, 4 emerged as the most potent against all of the tested parasites, but it was too toxic against host cells, hampering further studies. The retinoic 2′-aminoanilide 8 was less potent than 4 in all parasitic assays, but as its toxicity is considerably lower, it could be the starting structure for further development. In T. cruzi, compound 3 exhibited a single-digit micromolar inhibition of parasite growth combined with moderate toxicity. In S. mansoni, 4’s close analogs 17-20 were tested in new transformed schistosomula (NTS) and adult worms displaying high death induction against both parasite forms. Among them, 17 and 19 exhibited very low toxicity in human retinal pigment epithelial (RPE) cells, thus being promising compounds for further optimization.

https://pubmed.ncbi.nlm.nih.gov/35732073