Synthesis and Antitumor Effect in Vitro and in Vivo of Substituted 1,3-Dihydroindole-2-ones

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• 作者：Mette K. Christensen ; Kamille D. Erichsen ; Christina Trojel-Hansen ; Jette Tjø ; rnelund ; Sø ; ren J. Nielsen ; Karla Frydenvang ; Tommy N. Johansen ; Birgitte Nielsen ; Maxwell Sehested ; Peter B. Jens
• 刊名：Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：October 14, 2010
• 年：2010
• 卷：53
• 期：19
• 页码：7140-7145
• 全文大小：775K
• 年卷期：v.53,no.19(October 14, 2010)
• ISSN：1520-4804

文摘

Optimization of the anticancer activity for a class of compounds built on a 1,3-dihydroindole-2-one scaffold was performed. In comparison with recently published derivatives of oxyphenisatin the new analogues exhibited an equally potent antiproliferative activity in vitro and improved tolerability and activity in vivo. The best compounds from this series showed low nanomolar antiproliferative activity toward a series of cancer cell lines (compound (S)-38: IC₅₀ of 0.48 and 2 nM in MCF-7 (breast) and PC3 (prostate), respectively) and potent antitumor effects in well tolerated doses in xenograft models. The racemic compound (RS)-38 showed complete tumor regression at a dose of 20 mg/kg administered iv on days 1 and 7 in a PC3 rat xenograft.