@article{805c776b73b44590892fb854ea51f687,
title = "Unprecedented inhibition of P-gp activity by a novel ruthenium-cyclopentadienyl compound bearing a bipyridine-biotin ligand",
abstract = "Two new ruthenium complexes, [Ru(η5-Cp)(PPh3)(2,2{\textquoteright}-bipy-4,4{\textquoteright}-R)]+ with R = -CH2OH (Ru1) or dibiotin ester (Ru2) were synthesized and fully characterized. Both compounds were tested against two types of breast cancer cells (MCF7 and MDA-MB-231), showing better cytotoxicity than cisplatin in the same experimental conditions. Since multidrug resistance (MDR) is one of the main problems in cancer chemotherapy, we have assessed the potential of these compounds to overcome resistance to treatments. Ru2 showed exceptional selectivity as P-gp inhibitor, while Ru1 is possibly a substrate. In vivo studies in zebrafish showed that Ru2 is well tolerated up to 1.17 mg/L, presenting a LC50 of 5.73 mg/L at 5 days post fertilization.",
keywords = "Anticancer agents, Multidrug resistance, P-gp inhibitor, Ruthenium organometallic compounds",
author = "Leonor C{\^o}rte-Real and Brittany Karas and Patr{\'i}cia G{\'i}rio and Alexis Moreno and Fernando Avecilla and Fernanda Marques and Buckley, {Brian T.} and Cooper, {Keith R.} and Cathleen Doherty and Pierre Falson and Garcia, {M. Helena} and Andreia Valente",
note = "Funding Information: This work was financed by the Portuguese Foundation for Science and Technology (Funda{\c c}{\~a}o para a Ci{\^e}ncia e Tecnologia, FCT) within the scope of projects UID/QUI/00100/2013 and PTDC/QUI-QIN/28662/2017 . Andreia Valente acknowledges the Investigator FCT2013 Initiative for the project IF/01302/2013 (acknowledging FCT , as well as POPH and FSE - European Social Fund ). Leonor C{\^o}rte-Real thanks FCT for her Ph.D. Grant ( SFRH/BD/100515/2014 ) and Fulbright Research Grant 2017/2018 with the support of FCT. Brittany Karas thanks NJAES-RutgersNJ01201 , NIEHS Training Grant T32-ES 007148 and Brian Buckley, Cathleen Doherty NIEHS P30 ES005022 . Keith R. Cooper thanks NJAES Project 01202 (W2045), NIH ES005022 . Patr{\'i}cia G{\'i}rio was funded by the Erasmus + Program and a fellowship received from the French National Research Agency , ANR-13-BSV5-0001-01 (to Dr. Pierre Falson). Funding Information: This work was financed by the Portuguese Foundation for Science and Technology (Funda{\c c}{\~a}o para a Ci{\^e}ncia e Tecnologia, FCT) within the scope of projects UID/QUI/00100/2013 and PTDC/QUI-QIN/28662/2017. Andreia Valente acknowledges the Investigator FCT2013 Initiative for the project IF/01302/2013 (acknowledging FCT, as well as POPH and FSE - European Social Fund). Leonor C{\^o}rte-Real thanks FCT for her Ph.D. Grant (SFRH/BD/100515/2014) and Fulbright Research Grant 2017/2018 with the support of FCT. Brittany Karas thanks NJAES-RutgersNJ01201, NIEHS Training Grant T32-ES 007148 and Brian Buckley, Cathleen Doherty NIEHS P30 ES005022. Keith R. Cooper thanks NJAES Project 01202 (W2045), NIH ES005022. Patr{\'i}cia G{\'i}rio was funded by the Erasmus + Program and a fellowship received from the French National Research Agency, ANR-13-BSV5-0001-01 (to Dr. Pierre Falson). Publisher Copyright: {\textcopyright} 2018 Elsevier Masson SAS",
year = "2019",
month = feb,
day = "1",
doi = "10.1016/j.ejmech.2018.12.022",
language = "English (US)",
volume = "163",
pages = "853--863",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson SAS",
}