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

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

doi:10.1021/jm100763j

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

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

35 Citations (Scopus)

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.

Original language	English
Journal	Journal of Medicinal Chemistry
Volume	53
Issue number	19
Pages (from-to)	7140-7145
Number of pages	6
ISSN	0022-2623
DOIs	https://doi.org/10.1021/jm100763j
Publication status	Published - 14 Oct 2010

Keywords

Former Faculty of Pharmaceutical Sciences

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Christensen, M. K., Erichsen, K. D., Trojel-Hansen, C., Tjørnelund, J., Nielsen, S. J., Frydenvang, K. A., Johansen, T. N., Nielsen, B., Sehested, M., Jensen, P. B., Ikaunieks, M., Zaichenko, A., Loza, E., Kalvinsh, I., & Björkling, F. (2010). Synthesis and antitumor effect in vitro and in vivo of substituted 1,3-dihydroindole-2-ones. Journal of Medicinal Chemistry, 53(19), 7140-7145. https://doi.org/10.1021/jm100763j

Christensen, MK, Erichsen, KD, Trojel-Hansen, C, Tjørnelund, J, Nielsen, SJ, Frydenvang, KA , Johansen, TN , Nielsen, B, Sehested, M, Jensen, PB, Ikaunieks, M, Zaichenko, A, Loza, E, Kalvinsh, I & Björkling, F 2010, 'Synthesis and antitumor effect in vitro and in vivo of substituted 1,3-dihydroindole-2-ones', Journal of Medicinal Chemistry, vol. 53, no. 19, pp. 7140-7145. https://doi.org/10.1021/jm100763j

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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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AU - Christensen, Mette Knak

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AU - Tjørnelund, Jette

AU - Nielsen, Søren Jensby

AU - Frydenvang, Karla Andrea

AU - Johansen, Tommy Nørskov

AU - Nielsen, Birgitte

AU - Sehested, Maxwell

AU - Jensen, Peter Buhl

AU - Ikaunieks, Martins

AU - Zaichenko, Andrei

AU - Loza, Einars

AU - Kalvinsh, Ivars

AU - Björkling, Fredrik

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AB - 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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ER -

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

Abstract

Keywords

UN SDGs

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