Drug targeting to decrease cardiotoxicity - determination of the cytotoxic effect of GnRH-based conjugates containing doxorubicin, daunorubicin and methotrexate on human cardiomyocytes and endothelial cells

Beilstein Journal of Organic Chemistry
Livia PolgárLaszlo Kőhidai

Abstract

Background: Cardiomyopathy induced by the chemotherapeutic agents doxorubicin and daunorubicin is a major limiting factor for their application in cancer therapy. Chemotactic drug targeting potentially increases the tumor selectivity of drugs and decreases their cardiotoxicity. Increased expression of gonadotropin-releasing hormone (GnRH) receptors on the surface of tumor cells has been reported. Thus, the attachment of the aforementioned chemotherapeutic drugs to GnRH-based peptides may result in compounds with increased therapeutic efficacy. The objective of the present study was to examine the cytotoxic effect of anticancer drug-GnRH-conjugates against two essential cardiovascular cell types, such as cardiomyocytes and endothelial cells. Sixteen different previously developed GnRH-conjugates containing doxorubicin, daunorubicin and methotrexate were investigated in this study. Their cytotoxicity was determined on primary human cardiac myocytes (HCM) and human umbilical vein endothelial cells (HUVEC) using the xCELLigence SP system, which measures impedance changes caused by adhering cells on golden electrode arrays placed at the bottom of the wells. Slopes of impedance-time curves were calculated and for the quantitative det...Continue Reading

References

Jul 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·A NagyJ Horvath
Dec 26, 2001·European Journal of Endocrinology·Carsten GründkerGünter Emons
Oct 16, 2008·Current Medicinal Chemistry·Gábor MezoMagdolna Kovács
Dec 2, 2009·Expert Opinion on Drug Delivery·Gábor Mezo, Marilena Manea
Aug 26, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Pascal SchlageMarilena Manea
Apr 7, 2012·European Journal of Medicinal Chemistry·Ulrike LeursMarilena Manea
Jul 11, 2012·Endocrine Reviews·Patrizia LimontaRoberta M Moretti
Dec 5, 2012·Journal of Peptide Science : an Official Publication of the European Peptide Society·Eszter LajkóLászló Kőhidai
Feb 26, 2013·Bioorganic & Medicinal Chemistry Letters·Verena Natalie SchreierMarilena Manea

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Citations

Oct 31, 2020·Nucleic Acids Research·Balázs BaloghIstván M Mándity
Feb 6, 2020·Bioorganic Chemistry·Kinga PioreckaWlodzimierz A Stanczyk
Aug 28, 2020·International Journal of Biological Macromolecules·Balak Das KurmiShivani Rai Paliwal

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