Identification of a New Pentafluorosulfanyl-Substituted Chalcone with Activity Against Hepatoma and Human Parasites
Background/Objectives: New drugs are required for the treatment of liver cancers and protozoal parasite infections. Analogs of the known anticancer active and antileishmanial 2′,4′,6′-trimethoxychalcone SU086 were prepared and investigated. Methods: The chalcones were prepared according to the Clais...
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2025-01-01
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| author | Alessandra Viperino Michael Höpfner Nicole Edel Ibrahim S. Al Nasr Waleed S. Koko Tariq A. Khan Imen Ben Abdelmalek Rainer Schobert Bernhard Biersack Bianca Nitzsche |
| author_facet | Alessandra Viperino Michael Höpfner Nicole Edel Ibrahim S. Al Nasr Waleed S. Koko Tariq A. Khan Imen Ben Abdelmalek Rainer Schobert Bernhard Biersack Bianca Nitzsche |
| author_sort | Alessandra Viperino |
| collection | DOAJ |
| description | Background/Objectives: New drugs are required for the treatment of liver cancers and protozoal parasite infections. Analogs of the known anticancer active and antileishmanial 2′,4′,6′-trimethoxychalcone SU086 were prepared and investigated. Methods: The chalcones were prepared according to the Claisen–Schmidt condensation protocol and analyzed. They were tested for activity against two liver cancer cell lines (HepG2 and HuH-7) and protozoal parasites (<i>Toxoplasma gondii</i> and <i>Leishmania major</i>). Unspecific toxicity and expression of Hsp90 and Hsp70 upon treatment were analyzed in liver cancer cells. Results: A new chalcone, 2′,4′,6′-trimethoxy-3-pentafluorosulfanylchalcone (246TMP-3SF5), with a pentafluorosulfanyl (SF<sub>5</sub>) substituent showed pronounced activities against liver cancer cells and <i>T. gondii</i> parasites which were superior to the activities of the parent chalcone SU086 in these models. In contrast, SU086 and its anthracene analog 2′,4′,6′-trimethoxy-9-anthracenylchalcone (246TMP-Anth) were most active against <i>L. major</i> promastigotes. The new SF<sub>5</sub>-substituted chalcone behaved like the known Hsp90 inhibitor 17-AAG and upregulated Hsp70 expression in liver cancer cells. Conclusions: The SF<sub>5</sub>-substituted SU086 analog has potential to become a new drug for the therapy of hepatoma and toxoplasmosis. |
| format | Article |
| id | doaj-art-2f77142e64784cb084a01cdeda611e01 |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj-art-2f77142e64784cb084a01cdeda611e012025-01-24T13:45:11ZengMDPI AGPharmaceuticals1424-82472025-01-011815010.3390/ph18010050Identification of a New Pentafluorosulfanyl-Substituted Chalcone with Activity Against Hepatoma and Human ParasitesAlessandra Viperino0Michael Höpfner1Nicole Edel2Ibrahim S. Al Nasr3Waleed S. Koko4Tariq A. Khan5Imen Ben Abdelmalek6Rainer Schobert7Bernhard Biersack8Bianca Nitzsche9Institute of Physiology, Charité-Universitätsmedizin Berlin, Corporate Member of the Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, GermanyInstitute of Physiology, Charité-Universitätsmedizin Berlin, Corporate Member of the Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, GermanyInstitute of Physiology, Charité-Universitätsmedizin Berlin, Corporate Member of the Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, GermanyDepartment of Biology, College of Science, Qassim University, Qassim 51452, Saudi ArabiaDepartment of Biology, College of Science, Qassim University, Qassim 51452, Saudi ArabiaDepartment of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Ar Rass 51921, Saudi ArabiaDepartment of Biology, College of Science, Qassim University, Qassim 51452, Saudi ArabiaOrganic Chemistry Laboratory, University Bayreuth, Universitätsstrasse 30, 95440 Bayreuth, GermanyOrganic Chemistry Laboratory, University Bayreuth, Universitätsstrasse 30, 95440 Bayreuth, GermanyInstitute of Physiology, Charité-Universitätsmedizin Berlin, Corporate Member of the Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, GermanyBackground/Objectives: New drugs are required for the treatment of liver cancers and protozoal parasite infections. Analogs of the known anticancer active and antileishmanial 2′,4′,6′-trimethoxychalcone SU086 were prepared and investigated. Methods: The chalcones were prepared according to the Claisen–Schmidt condensation protocol and analyzed. They were tested for activity against two liver cancer cell lines (HepG2 and HuH-7) and protozoal parasites (<i>Toxoplasma gondii</i> and <i>Leishmania major</i>). Unspecific toxicity and expression of Hsp90 and Hsp70 upon treatment were analyzed in liver cancer cells. Results: A new chalcone, 2′,4′,6′-trimethoxy-3-pentafluorosulfanylchalcone (246TMP-3SF5), with a pentafluorosulfanyl (SF<sub>5</sub>) substituent showed pronounced activities against liver cancer cells and <i>T. gondii</i> parasites which were superior to the activities of the parent chalcone SU086 in these models. In contrast, SU086 and its anthracene analog 2′,4′,6′-trimethoxy-9-anthracenylchalcone (246TMP-Anth) were most active against <i>L. major</i> promastigotes. The new SF<sub>5</sub>-substituted chalcone behaved like the known Hsp90 inhibitor 17-AAG and upregulated Hsp70 expression in liver cancer cells. Conclusions: The SF<sub>5</sub>-substituted SU086 analog has potential to become a new drug for the therapy of hepatoma and toxoplasmosis.https://www.mdpi.com/1424-8247/18/1/50chalconeanticancer agentantiparasitic agentliver cancerleishmaniasistoxoplasmosis |
| spellingShingle | Alessandra Viperino Michael Höpfner Nicole Edel Ibrahim S. Al Nasr Waleed S. Koko Tariq A. Khan Imen Ben Abdelmalek Rainer Schobert Bernhard Biersack Bianca Nitzsche Identification of a New Pentafluorosulfanyl-Substituted Chalcone with Activity Against Hepatoma and Human Parasites Pharmaceuticals chalcone anticancer agent antiparasitic agent liver cancer leishmaniasis toxoplasmosis |
| title | Identification of a New Pentafluorosulfanyl-Substituted Chalcone with Activity Against Hepatoma and Human Parasites |
| title_full | Identification of a New Pentafluorosulfanyl-Substituted Chalcone with Activity Against Hepatoma and Human Parasites |
| title_fullStr | Identification of a New Pentafluorosulfanyl-Substituted Chalcone with Activity Against Hepatoma and Human Parasites |
| title_full_unstemmed | Identification of a New Pentafluorosulfanyl-Substituted Chalcone with Activity Against Hepatoma and Human Parasites |
| title_short | Identification of a New Pentafluorosulfanyl-Substituted Chalcone with Activity Against Hepatoma and Human Parasites |
| title_sort | identification of a new pentafluorosulfanyl substituted chalcone with activity against hepatoma and human parasites |
| topic | chalcone anticancer agent antiparasitic agent liver cancer leishmaniasis toxoplasmosis |
| url | https://www.mdpi.com/1424-8247/18/1/50 |
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