Enhanced enzymatic stability and antitumor activity of daunorubicin-GnRH-III bioconjugates modified in position 4

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Standard

Enhanced enzymatic stability and antitumor activity of daunorubicin-GnRH-III bioconjugates modified in position 4. / Manea, Marilena; Leurs, Ulrike; Orbán, Erika; Baranyai, Zsuzsa; Öhlschläger, Peter; Marquardt, Andreas; Schulcz, Ákos; Tejeda, Miguel; Kapuvári, Bence; Tóvári, József; Mezo, Gábor.

I: Bioconjugate Chemistry, Bind 22, Nr. 7, 20.07.2011, s. 1320-9.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Manea, M, Leurs, U, Orbán, E, Baranyai, Z, Öhlschläger, P, Marquardt, A, Schulcz, Á, Tejeda, M, Kapuvári, B, Tóvári, J & Mezo, G 2011, 'Enhanced enzymatic stability and antitumor activity of daunorubicin-GnRH-III bioconjugates modified in position 4', Bioconjugate Chemistry, bind 22, nr. 7, s. 1320-9. https://doi.org/10.1021/bc100547p

APA

Manea, M., Leurs, U., Orbán, E., Baranyai, Z., Öhlschläger, P., Marquardt, A., Schulcz, Á., Tejeda, M., Kapuvári, B., Tóvári, J., & Mezo, G. (2011). Enhanced enzymatic stability and antitumor activity of daunorubicin-GnRH-III bioconjugates modified in position 4. Bioconjugate Chemistry, 22(7), 1320-9. https://doi.org/10.1021/bc100547p

Vancouver

Manea M, Leurs U, Orbán E, Baranyai Z, Öhlschläger P, Marquardt A o.a. Enhanced enzymatic stability and antitumor activity of daunorubicin-GnRH-III bioconjugates modified in position 4. Bioconjugate Chemistry. 2011 jul. 20;22(7):1320-9. https://doi.org/10.1021/bc100547p

Author

Manea, Marilena ; Leurs, Ulrike ; Orbán, Erika ; Baranyai, Zsuzsa ; Öhlschläger, Peter ; Marquardt, Andreas ; Schulcz, Ákos ; Tejeda, Miguel ; Kapuvári, Bence ; Tóvári, József ; Mezo, Gábor. / Enhanced enzymatic stability and antitumor activity of daunorubicin-GnRH-III bioconjugates modified in position 4. I: Bioconjugate Chemistry. 2011 ; Bind 22, Nr. 7. s. 1320-9.

Bibtex

@article{0b7410389e8a4ce28e2767b107dbd01b,
title = "Enhanced enzymatic stability and antitumor activity of daunorubicin-GnRH-III bioconjugates modified in position 4",
abstract = "Here, we report on the synthesis, enzymatic stability, and antitumor activity of novel bioconjugates containing the chemotherapeutic agent daunorubicin attached through an oxime bond to various gonadotropin-releasing hormone-III (GnRH-III) derivatives. In order to increase the enzymatic stability of the bioconjugates (in particular against chymotrypsin), (4)Ser was replaced by N-Me-Ser or Lys(Ac). A compound in which (4)Lys was not acetylated was also prepared, with the aim of investigating the influence of the free ε-amino group on the biochemical properties. The in vitro cytostatic effect of the bioconjugates was determined on MCF-7 human breast, HT-29 human colon, and LNCaP human prostate cancer cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Their stability/degradation (1) in human serum, (2) in the presence of rat liver lysosomal homogenate, and (3) in the presence of digestive enzymes (trypsin, chymotrypsin, and pepsin) was analyzed by liquid chromatography in combination with mass spectrometry. The results showed that (1) all synthesized bioconjugates had in vitro cytostatic effect, (2) they were stable in human serum at least for 24 h, and (3) they were hydrolyzed in the presence of lysosomal homogenate. All compounds were stable in the presence of (1) pepsin and (2) trypsin (except for the (4)Lys containing bioconjugate). In the presence of chymotrypsin, all bioconjugates were digested; the degradation rate strongly depending on their structure. The bioconjugates in which (4)Ser was replaced by N-Me-Ser or Lys(Ac) had the highest enzymatic stability, making them potential candidates for oral administration. In vivo tumor growth inhibitory effect of two selected bioconjugates was evaluated on orthotopically developed C26 murine colon carcinoma bearing mice. The results indicated that the compound containing Lys(Ac) in position 4 had significantly higher antitumor activity than the parent bioconjugate.",
author = "Marilena Manea and Ulrike Leurs and Erika Orb{\'a}n and Zsuzsa Baranyai and Peter {\"O}hlschl{\"a}ger and Andreas Marquardt and {\'A}kos Schulcz and Miguel Tejeda and Bence Kapuv{\'a}ri and J{\'o}zsef T{\'o}v{\'a}ri and G{\'a}bor Mezo",
year = "2011",
month = jul,
day = "20",
doi = "10.1021/bc100547p",
language = "English",
volume = "22",
pages = "1320--9",
journal = "Bioconjugate Chemistry",
issn = "1043-1802",
publisher = "American Chemical Society",
number = "7",

}

RIS

TY - JOUR

T1 - Enhanced enzymatic stability and antitumor activity of daunorubicin-GnRH-III bioconjugates modified in position 4

AU - Manea, Marilena

AU - Leurs, Ulrike

AU - Orbán, Erika

AU - Baranyai, Zsuzsa

AU - Öhlschläger, Peter

AU - Marquardt, Andreas

AU - Schulcz, Ákos

AU - Tejeda, Miguel

AU - Kapuvári, Bence

AU - Tóvári, József

AU - Mezo, Gábor

PY - 2011/7/20

Y1 - 2011/7/20

N2 - Here, we report on the synthesis, enzymatic stability, and antitumor activity of novel bioconjugates containing the chemotherapeutic agent daunorubicin attached through an oxime bond to various gonadotropin-releasing hormone-III (GnRH-III) derivatives. In order to increase the enzymatic stability of the bioconjugates (in particular against chymotrypsin), (4)Ser was replaced by N-Me-Ser or Lys(Ac). A compound in which (4)Lys was not acetylated was also prepared, with the aim of investigating the influence of the free ε-amino group on the biochemical properties. The in vitro cytostatic effect of the bioconjugates was determined on MCF-7 human breast, HT-29 human colon, and LNCaP human prostate cancer cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Their stability/degradation (1) in human serum, (2) in the presence of rat liver lysosomal homogenate, and (3) in the presence of digestive enzymes (trypsin, chymotrypsin, and pepsin) was analyzed by liquid chromatography in combination with mass spectrometry. The results showed that (1) all synthesized bioconjugates had in vitro cytostatic effect, (2) they were stable in human serum at least for 24 h, and (3) they were hydrolyzed in the presence of lysosomal homogenate. All compounds were stable in the presence of (1) pepsin and (2) trypsin (except for the (4)Lys containing bioconjugate). In the presence of chymotrypsin, all bioconjugates were digested; the degradation rate strongly depending on their structure. The bioconjugates in which (4)Ser was replaced by N-Me-Ser or Lys(Ac) had the highest enzymatic stability, making them potential candidates for oral administration. In vivo tumor growth inhibitory effect of two selected bioconjugates was evaluated on orthotopically developed C26 murine colon carcinoma bearing mice. The results indicated that the compound containing Lys(Ac) in position 4 had significantly higher antitumor activity than the parent bioconjugate.

AB - Here, we report on the synthesis, enzymatic stability, and antitumor activity of novel bioconjugates containing the chemotherapeutic agent daunorubicin attached through an oxime bond to various gonadotropin-releasing hormone-III (GnRH-III) derivatives. In order to increase the enzymatic stability of the bioconjugates (in particular against chymotrypsin), (4)Ser was replaced by N-Me-Ser or Lys(Ac). A compound in which (4)Lys was not acetylated was also prepared, with the aim of investigating the influence of the free ε-amino group on the biochemical properties. The in vitro cytostatic effect of the bioconjugates was determined on MCF-7 human breast, HT-29 human colon, and LNCaP human prostate cancer cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Their stability/degradation (1) in human serum, (2) in the presence of rat liver lysosomal homogenate, and (3) in the presence of digestive enzymes (trypsin, chymotrypsin, and pepsin) was analyzed by liquid chromatography in combination with mass spectrometry. The results showed that (1) all synthesized bioconjugates had in vitro cytostatic effect, (2) they were stable in human serum at least for 24 h, and (3) they were hydrolyzed in the presence of lysosomal homogenate. All compounds were stable in the presence of (1) pepsin and (2) trypsin (except for the (4)Lys containing bioconjugate). In the presence of chymotrypsin, all bioconjugates were digested; the degradation rate strongly depending on their structure. The bioconjugates in which (4)Ser was replaced by N-Me-Ser or Lys(Ac) had the highest enzymatic stability, making them potential candidates for oral administration. In vivo tumor growth inhibitory effect of two selected bioconjugates was evaluated on orthotopically developed C26 murine colon carcinoma bearing mice. The results indicated that the compound containing Lys(Ac) in position 4 had significantly higher antitumor activity than the parent bioconjugate.

U2 - 10.1021/bc100547p

DO - 10.1021/bc100547p

M3 - Journal article

C2 - 21668011

VL - 22

SP - 1320

EP - 1329

JO - Bioconjugate Chemistry

JF - Bioconjugate Chemistry

SN - 1043-1802

IS - 7

ER -

ID: 45967511