Design and Synthesis of 1,3-Diarylpyrazoles and Investigation of Their Cytotoxicity and Antiparasitic Profile

• Published in: International journal of molecular sciences Vol. 25; no. 9; p. 4693
• Main Authors: Bozdag, Murat, Mertens, Freke, Matheeussen, An, Van Pelt, Natascha, Foubert, Kenn, Hermans, Nina, De Meyer, Guido R Y, Augustyns, Koen, Martinet, Wim, Caljon, Guy, Van der Veken, Pieter
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.05.2024
• Subjects: 1,3-diarylpyrazole; Acids; antiparasitic activity; Antiparasitic Agents - chemical synthesis; Antiparasitic Agents - chemistry; Antiparasitic Agents - pharmacology; Antiprotozoal Agents - chemical synthesis; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacology; Autophagy; Cells; Chemistry; Crizotinib; Cytotoxicity; Drug Design; Gram-positive bacteria; Humans; Investigations; Kinases; Leishmania infantum - drug effects; Nonsteroidal anti-inflammatory drugs; Permeability; pyrazole; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; Stanozolol; Structure-Activity Relationship; Tropical diseases; Trypanosoma brucei rhodesiense - drug effects; Trypanosoma cruzi - drug effects; Belgium; pyrazole; antiparasitic activity; 1,3-diarylpyrazole; cytotoxicity
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25094693

Herein, we report a series of 1,3-diarylpyrazoles that are analogues of compound /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 , , and . The most interesting compounds displayed low micromolar whole-cell potencies against individual or several parasitic species, while lacking cytotoxicity against human cells.