Identification of a New Pentafluorosulfanyl-Substituted Chalcone with Activity Against Hepatoma and Human Parasites.

IF 4.3 3区医学 Q2 CHEMISTRY, MEDICINAL

Pharmaceuticals Pub Date : 2025-01-03 DOI:10.3390/ph18010050

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

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引用次数: 0

Abstract

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 (Toxoplasma gondii and Leishmania major). 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 (SF₅) substituent showed pronounced activities against liver cancer cells and T. gondii 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 L. major promastigotes. The new SF₅-substituted chalcone behaved like the known Hsp90 inhibitor 17-AAG and upregulated Hsp70 expression in liver cancer cells.

Conclusions: The SF₅-substituted SU086 analog has potential to become a new drug for the therapy of hepatoma and toxoplasmosis.

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来源期刊

Pharmaceuticals Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

CiteScore

6.10

自引率

4.30%

发文量

1332

审稿时长

6 weeks

期刊介绍： Pharmaceuticals (ISSN 1424-8247) is an international scientific journal of medicinal chemistry and related drug sciences.Our aim is to publish updated reviews as well as research articles with comprehensive theoretical and experimental details. Short communications are also accepted; therefore, there is no restriction on the maximum length of the papers.