Document Report Card

ID: ALA1255220

Journal: J Med Chem

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

Authors: Christensen MK, Erichsen KD, Trojel-Hansen C, Tjørnelund J, Nielsen SJ, Frydenvang K, Johansen TN, Nielsen B, Sehested M, Jensen PB, Ikaunieks M, Zaichenko A, Loza E, Kalvinsh I, Björkling F.

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.

CiteXplore: 20845961

DOI: 10.1021/jm100763j