Chemically Diverse S. mansoni HDAC8 Inhibitors Reduce Viability in Worm Larval and Adult Stages.


Journal

ChemMedChem
ISSN: 1860-7187
Titre abrégé: ChemMedChem
Pays: Germany
ID NLM: 101259013

Informations de publication

Date de publication:
01 02 2023
Historique:
revised: 16 10 2022
received: 21 09 2022
pubmed: 18 10 2022
medline: 8 2 2023
entrez: 17 10 2022
Statut: ppublish

Résumé

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 IC

Identifiants

pubmed: 36250286
doi: 10.1002/cmdc.202200510
doi:

Substances chimiques

HDAC8 protein, human EC 3.5.1.98
Histone Deacetylase Inhibitors 0
Histone Deacetylases EC 3.5.1.98
Repressor Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e202200510

Informations de copyright

© 2022 Wiley-VCH GmbH.

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Auteurs

Beatrice Noce (B)

Department of Drug Chemistry and Technologies, Sapienza University of Rome, 00185, Rome, Italy.

Elisabetta Di Bello (E)

Department of Drug Chemistry and Technologies, Sapienza University of Rome, 00185, Rome, Italy.

Clemens Zwergel (C)

Department of Drug Chemistry and Technologies, Sapienza University of Rome, 00185, Rome, Italy.

Rossella Fioravanti (R)

Department of Drug Chemistry and Technologies, Sapienza University of Rome, 00185, Rome, Italy.

Sergio Valente (S)

Department of Drug Chemistry and Technologies, Sapienza University of Rome, 00185, Rome, Italy.

Dante Rotili (D)

Department of Drug Chemistry and Technologies, Sapienza University of Rome, 00185, Rome, Italy.

Andrea Masotti (A)

Research Laboratories, Bambino Gesù Children's Hospital-IRCCS, 00146, Rome, Italy.

Mohammad Salik Zeya Ansari (M)

Institute of Molecular Biology and Pathology, National Research Council (CNR), 00185, Rome, Italy.

Daniela Trisciuoglio (D)

Institute of Molecular Biology and Pathology, National Research Council (CNR), 00185, Rome, Italy.

Alokta Chakrabarti (A)

Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, 79104, Freiburg, Germany.

Christophe Romier (C)

Département de Biologie Structurale Intégrative, Institut de Génétique et Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg, CNRS, INSERM, 67404, Illkirch Cedex, France.

Dina Robaa (D)

Institute of Pharmacy, Martin Luther University of Halle-Wittenberg, 06120, Halle (Saale), Germany.

Wolfgang Sippl (W)

Institute of Pharmacy, Martin Luther University of Halle-Wittenberg, 06120, Halle (Saale), Germany.

Manfred Jung (M)

Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, 79104, Freiburg, Germany.

Cécile Häberli (C)

Swiss Tropical and Public Health Institute, 4123, Allschwil, Switzerland.
University of Basel, Basel, 4001, Switzerland.

Jennifer Keiser (J)

Swiss Tropical and Public Health Institute, 4123, Allschwil, Switzerland.
University of Basel, Basel, 4001, Switzerland.

Antonello Mai (A)

Department of Drug Chemistry and Technologies, Sapienza University of Rome, 00185, Rome, Italy.
Pasteur Institute, Cenci-Bolognetti Foundation, Sapienza University of Rome, 00185, Rome, Italy.

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