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
摘要
背景/目的：肝癌和原生动物寄生虫感染的治疗需要新药。对已知的具有抗癌活性和抗利什曼病活性的2',4',6'-三甲氧基查尔酮SU086的类似物进行了制备和研究。方法：采用Claisen-Schmidt缩合法制备查尔酮，并对其进行分析。检测了它们对两种肝癌细胞系（HepG2和HuH-7）和原生动物寄生虫（刚地弓形虫和利什曼原虫）的活性。分析了Hsp90和Hsp70在肝癌细胞中的非特异性毒性和表达情况。结果：新查尔酮2',4',6'-三甲氧基-3-五氟磺胺基查尔酮（246TMP-3SF5），含五氟磺胺基（SF5）取代基，对肝癌细胞和弓形虫具有明显的抗肿瘤活性，其活性优于亲本查尔酮SU086。而SU086及其蒽类似物2',4',6'-三甲氧基-9-蒽基查尔酮（246TMP-Anth）对L. major promastigotes的抑菌活性最强。新的sf5取代查尔酮表现出与已知的Hsp90抑制剂17-AAG相似的行为，并上调肝癌细胞中Hsp70的表达。结论：sf5取代的SU086类似物有潜力成为治疗肝癌和弓形虫病的新药。
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 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.
PharmaceuticalsPharmacology, 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.
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