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

oleh: Murat Bozdag, Freke Mertens, An Matheeussen, Natascha Van Pelt, Kenn Foubert, Nina Hermans, Guido R. Y. De Meyer, Koen Augustyns, Wim Martinet, Guy Caljon, Pieter Van der Veken

Format: Article
Diterbitkan: MDPI AG 2024-04-01

Deskripsi

Herein, we report a series of 1,3-diarylpyrazoles that are analogues of compound <b>26</b>/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 <i>Trypanosoma cruzi</i>, <i>T. brucei rhodesiense</i>, and <i>Leishmania infantum</i>. The most interesting compounds displayed low micromolar whole-cell potencies against individual or several parasitic species, while lacking cytotoxicity against human cells.