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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Mette Knak Christensen, Kamille Dumong Erichsen, Christina Trojel-Hansen, Jette Tjørnelund, Søren Jensby Nielsen, Karla Andrea Frydenvang, Tommy Nørskov Johansen, Birgitte Nielsen, Maxwell Sehested, Peter Buhl Jensen, Martins Ikaunieks, Andrei Zaichenko, Einars Loza, Ivars Kalvinsh, Fredrik Björkling

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.
OriginalsprogEngelsk
TidsskriftJournal of Medicinal Chemistry
Vol/bind53
Udgave nummer19
Sider (fra-til)7140-7145
Antal sider6
ISSN0022-2623
DOI
StatusUdgivet - 14 okt. 2010

ID: 32330717