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Chemically diverse S. mansoni HDAC8 inhibitors reduced viability in worm larval and adult stages

Noce, B. and Di Bello, E. and Zwergel, C. and Fioravanti, R. and Valente, S. and Rotili, D. and Masotti, A. and Ansari, M. S. Z. and Trisciuoglio, D. and Chakrabarti, A. and Romier, C. and Robaa, D. and Sippl, W. and Jung, M. and Häberli, C. and Keiser, J. and Mai, A.. (2022) Chemically diverse S. mansoni HDAC8 inhibitors reduced viability in worm larval and adult stages. ChemMedChem. In press.

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Official URL: https://edoc.unibas.ch/90961/

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Abstract

Schistosoma mansoni HDAC8 is a reliable target to fight schistosomiasis, and several inhibitors have been reported in the literature up to now. Nevertheless, only a few displayed selectivity over the human deacetylases and some exhibited very low or no activity against parasite larvae and/or adult worms. We report here the in vitro enzyme and biological activity of a small library of HDAC inhibitors from our lab, in many cases exhibiting submicromolar/nanomolar potency against smHDAC8 and diverse degrees of selectivity over hHDAC1 and/or hHDAC6. Such compounds were tested against schistosomula, and a selection of them against the adult forms of S. mansoni, to detect their effect on viability. Some of them showed the highest viability reduction for the larval stage with IC50 values around 1 microM and/or displayed ~ 40-50% activity in adult worms at 10 microM, joined to moderate to no toxicity in human fibroblast MRC-5 cells.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Helminth Drug Development (Keiser)
UniBasel Contributors:Häberli, Cécile and Keiser, Jennifer
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1860-7187 (Electronic)1860-7179 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:27 Dec 2022 16:11
Deposited On:27 Dec 2022 16:11

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