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 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Journal of Medicinal Chemistry
Vol/bind	53
Udgave nummer	19
Sider (fra-til)	7140-7145
Antal sider	6
ISSN	0022-2623
DOI	https://doi.org/10.1021/jm100763j
Status	Udgivet - 14 okt. 2010

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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, bind 53, nr. 19, s. 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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author = "Christensen, {Mette Knak} and Erichsen, {Kamille Dumong} and Christina Trojel-Hansen and Jette Tj{\o}rnelund and Nielsen, {S{\o}ren Jensby} and Frydenvang, {Karla Andrea} and Johansen, {Tommy N{\o}rskov} and Birgitte Nielsen and Maxwell Sehested and Jensen, {Peter Buhl} and Martins Ikaunieks and Andrei Zaichenko and Einars Loza and Ivars Kalvinsh and Fredrik Bj{\"o}rkling",

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AU - Christensen, Mette Knak

AU - Erichsen, Kamille Dumong

AU - Trojel-Hansen, Christina

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

PY - 2010/10/14

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N2 - 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.

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.

KW - Former Faculty of Pharmaceutical Sciences

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ER -

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

Abstract

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