2. Academic Validation
  3. Synthesis and antitumor effect in vitro and in vivo of substituted 1,3-dihydroindole-2-ones

Synthesis and antitumor effect in vitro and in vivo of substituted 1,3-dihydroindole-2-ones

  • J Med Chem. 2010 Oct 14;53(19):7140-5. doi: 10.1021/jm100763j.
Mette K Christensen 1,  Kamille D Erichsen,  Christina Trojel-Hansen,  Jette Tjørnelund,  Søren J Nielsen,  Karla Frydenvang,  Tommy N Johansen,  Birgitte Nielsen,  Maxwell Sehested,  Peter B Jensen,  Martins Ikaunieks,  Andrei Zaichenko,  Einars Loza,  Ivars Kalvinsh,  Fredrik Björkling
Affiliations

Affiliation

  • 1 TopoTarget A/S, Symbion, Fruebjergvej 3, DK-2100 Copenhagen, Denmark.
PMID: 20845961 DOI: 10.1021/jm100763j
Abstract

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: IC(50) 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.

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