Design and Synthesis of 1,3-Diarylpyrazoles and Investigation of Their Cytotoxicity and Antiparasitic Profile
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Published:2024-04-25
Issue:9
Volume:25
Page:4693
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Bozdag Murat1ORCID, Mertens Freke2ORCID, Matheeussen An3ORCID, Van Pelt Natascha3ORCID, Foubert Kenn4ORCID, Hermans Nina4ORCID, De Meyer Guido R. Y.2ORCID, Augustyns Koen1, Martinet Wim2ORCID, Caljon Guy3ORCID, Van der Veken Pieter1
Affiliation:
1. Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, Infla-Med Centre of Excellence, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk-Antwerp, Belgium 2. Laboratory of Physiopharmacology, Department of Pharmaceutical Sciences, Infla-Med Centre of Excellence, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk-Antwerp, Belgium 3. Laboratory of Microbiology, Parasitology and Hygiene, Department of Biomedical Sciences, Infla-Med Centre of Excellence, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk-Antwerp, Belgium 4. Natural Products and Food Research and Analysis–Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk-Antwerp, Belgium
Abstract
Herein, we report a series of 1,3-diarylpyrazoles that are analogues of compound 26/HIT 8. We previously identified this molecule as a ‘hit’ during a high-throughput screening campaign for autophagy inducers. A variety of synthetic strategies were utilized to modify the 1,3-diarylpyrazole core at its 1-, 3-, and 4-position. Compounds were assessed in vitro to identify their cytotoxicity properties. Of note, several compounds in the series displayed relevant cytotoxicity, which warrants scrutiny while interpreting biological activities that have been reported for structurally related molecules. In addition, antiparasitic activities were recorded against a range of human-infective protozoa, including Trypanosoma cruzi, T. brucei rhodesiense, and Leishmania infantum. The most interesting compounds displayed low micromolar whole-cell potencies against individual or several parasitic species, while lacking cytotoxicity against human cells.
Funder
Research Foundation—Flanders University of Antwerp
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