Synthesis, anticancer evaluation and pharmacokinetic study of novel 10-O-phenyl ethers of dihydroartemisinin.

European Journal of Medicinal Chemistry
Shenglin LuanLinxiang Zhao

Abstract

Twenty hybrid compounds, tethering dihydroartemisinin (DHA) with diaryl-pyrazoline/diaryl-pyrazole through ether linkage, were synthesized based on hybridization strategy and assessed for their anticancer activity. The representative compound 6f exhibited significantly elevated antiproliferative activity compared with DHA against a panel of cancer cell lines. Unexpected sensitivity of 6f in Adriamycin-resistant MCF-7 cells (MCF-7/Adr) inspired subsequent research on anticancer activity of these DHA derivatives against breast cancer cell lines. All the novel compounds exhibited potent activity in three breast cancer cells including MDA-MB-231, MCF-7 and MCF-7/Adr. Most of them exerted almost 10-fold higher potency in MCF-7/Adr than in MCF-7 and MDA-MB-231 cells. Compound 5f, the most potent compound against MCF-7/Adr (GI50 = 18 nM), was used for mechanism research which revealed that compound 5f arrested MCF-7 and MCF-7/Adr cells in G0/G1 phase with decreased levels of cyclin D1 and increased levels of p27. Preliminary pharmacokinetic properties of 5f and 6f were investigated in rats after a single intravenous administration. The high sensitivity of MCF-7/Adr indicates that these compounds have potential to be developed as thera...Continue Reading

References

Sep 11, 2007·Bioorganic & Medicinal Chemistry Letters·Marlie JohnsonMoses Lee
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Citations

Sep 3, 2019·Current Pharmaceutical Design·Maushmi S KumarMayur C Yergeri
Apr 11, 2018·Natural Products and Bioprospecting·Yunqin ZhangZhili Zuo
Aug 8, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Leydi M MorenoBraulio Insuasty
Aug 6, 2020·International Journal of Molecular Sciences·Dimitris Matiadis, Marina Sagnou

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