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Antiproliferation and Antiencystation Effect of Class II Histone Deacetylase Inhibitors on .

Authors:
Ki-Back Chu Hae-Ahm Lee Marc Pflieger Fabian Fischer Yodita Asfaha Leandro A Alves Avelar Alexander Skerhut Matthias U Kassack Finn K Hansen Andrea Schöler Thomas Kurz Min-Jeong Kim Eun-Kyung Moon Fu-Shi Quan

ACS Infect Dis 2022 02 7;8(2):271-279. Epub 2022 Jan 7.

Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, 02447 Seoul, South Korea.

is a ubiquitous and free-living protozoan pathogen responsible for causing keratitis (AK), a severe corneal infection inflicting immense pain that can result in permanent blindness. A drug-based treatment of AK has remained arduous because trophozoites undergo encystment to become highly drug-resistant cysts upon exposure to harsh environmental conditions such as amoebicidal agents (e.g., polyhexanide, chloroquine, and chlorohexidine). As such, drugs that block the encystation process could result in a successful AK treatment. Histone deacetylase inhibitors (HDACi) have recently emerged as novel therapeutic options for treating various protozoan and parasitic diseases. Here, we investigated whether novel HDACi suppress the proliferation and encystation of . Synthetic class II HDACi FFK29 (IIa selective) and MPK576 (IIb selective) dose-dependently decreased the viability of trophozoites. While these HDACi demonstrated a negligible effect on the viability of mature cysts, encystation was significantly inhibited by these HDACi. Apoptosis was slightly increased in trophozoites after a treatment with these HDACi, whereas cysts were unaffected by the HDACi exposure. The viability of human corneal cells was not affected by HDACi concentrations up to 10 μmol/L. In conclusion, these synthetic HDACi demonstrated potent amoebicidal effects and inhibited the growth and encystation of , thus highlighting their enormous potential for further development.

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http://dx.doi.org/10.1021/acsinfecdis.1c00390DOI Listing
February 2022

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