Viperino Alessandra, Höpfner Michael, Edel Nicole, Al Nasr Ibrahim S, Koko Waleed S, Khan Tariq A, Ben Abdelmalek Imen, Schobert Rainer, Biersack Bernhard, Nitzsche Bianca
Institute 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, Germany.
Department of Biology, College of Science, Qassim University, Qassim 51452, Saudi Arabia.
Pharmaceuticals (Basel). 2025 Jan 3;18(1):50. doi: 10.3390/ph18010050.
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.
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 ( and ). Unspecific toxicity and expression of Hsp90 and Hsp70 upon treatment were analyzed in liver cancer cells.
A new chalcone, 2',4',6'-trimethoxy-3-pentafluorosulfanylchalcone (246TMP-3SF5), with a pentafluorosulfanyl (SF) substituent showed pronounced activities against liver cancer cells and 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 promastigotes. The new SF-substituted chalcone behaved like the known Hsp90 inhibitor 17-AAG and upregulated Hsp70 expression in liver cancer cells.
The SF-substituted SU086 analog has potential to become a new drug for the therapy of hepatoma and toxoplasmosis.
背景/目的：肝癌和原生动物寄生虫感染的治疗需要新型药物。制备并研究了已知的抗癌活性和抗利什曼原虫的2',4',6'-三甲氧基查耳酮SU086的类似物。
根据克莱森-施密特缩合方案制备并分析查耳酮。测试它们对两种肝癌细胞系（HepG2和HuH-7）和原生动物寄生虫（及）的活性。分析肝癌细胞经处理后的非特异性毒性以及Hsp90和Hsp70的表达。
一种带有五氟硫烷基（SF）取代基的新型查耳酮，2',4',6'-三甲氧基-3-五氟硫烷基查耳酮（246TMP-3SF5），在这些模型中对肝癌细胞和寄生虫显示出显著活性，优于母体查耳酮SU086的活性。相比之下，SU086及其蒽类似物2',4',6'-三甲氧基-9-蒽基查耳酮（246TMP-Anth）对前鞭毛体最具活性。这种新的SF取代查耳酮的行为类似于已知的Hsp90抑制剂17-AAG，并上调肝癌细胞中Hsp70的表达。
SF取代的SU086类似物有潜力成为治疗肝癌和弓形虫病的新药。
