caa a22 4500 605507147 CHVBK 20210128100630.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s00775-015-1290-2 doi (NATIONALLICENCE)springer-10.1007/s00775-015-1290-2 Evaluation of fluorophore-tethered platinum complexes to monitor the fate of cisplatin analogs [Elektronische Daten] [Justin Jagodinsky, Agnieszka Sulima, Yiqi Cao, Joanna Poprawski, Burchelle Blackman, John Lloyd, Rolf Swenson, Michael Gottesman, Matthew Hall] The platinum drugs cisplatin, carboplatin, and oxaliplatin are highly utilized in the clinic and as a consequence have been extensively studied in the laboratory setting, sometimes by generating fluorophore-tagged analogs. Here, we synthesized two Pt(II) complexes containing ethane-1,2-diamine ligands linked to a BODIPY fluorophore, and compared their biological activity with previously reported Pt(II) complexes conjugated to carboxyfluorescein and carboxyfluorescein diacetate. The cytotoxicity and DNA damage capacity of Pt-fluorophore complexes was compared to cisplatin, and the Pt-BODIPY complexes were found to be more cytotoxic with reduced cytotoxicity in cisplatin-resistant cells. Microscopy revealed a predominately cytosolic localization, with nuclear distribution at higher concentrations. Spheroids grown from parent and resistant cells revealed penetration of Pt-BODIPY into spheroids, and retention of the cisplatin-resistant spheroid phenotype. While most activity profiles were retained for the Pt-BODIPY complexes, accumulation in resistant cells was only slightly affected, suggesting that some aspects of Pt-fluorophore cellular pharmacology deviate from cisplatin. SBIC (outside the USA), 2015 Accumulation nationallicence Trafficking nationallicence Platinum nationallicence Resistance nationallicence Jagodinsky Justin Laboratory of Cell Biology, National Cancer Institute, Center for Cancer Research, National Institutes of Health, 37 Convent Drive, Rm. 2108, 20892, Bethesda, MD, USA aut Sulima Agnieszka Imaging Probe Development Center, National Institutes of Health, Rockville, MD, USA aut Cao Yiqi Laboratory of Cell Biology, National Cancer Institute, Center for Cancer Research, National Institutes of Health, 37 Convent Drive, Rm. 2108, 20892, Bethesda, MD, USA aut Poprawski Joanna Laboratory of Cell Biology, National Cancer Institute, Center for Cancer Research, National Institutes of Health, 37 Convent Drive, Rm. 2108, 20892, Bethesda, MD, USA aut Blackman Burchelle Imaging Probe Development Center, National Institutes of Health, Rockville, MD, USA aut Lloyd John Advanced Mass Spectrometry Facility, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 20892, Bethesda, MD, USA aut Swenson Rolf Imaging Probe Development Center, National Institutes of Health, Rockville, MD, USA aut Gottesman Michael Laboratory of Cell Biology, National Cancer Institute, Center for Cancer Research, National Institutes of Health, 37 Convent Drive, Rm. 2108, 20892, Bethesda, MD, USA aut Hall Matthew Laboratory of Cell Biology, National Cancer Institute, Center for Cancer Research, National Institutes of Health, 37 Convent Drive, Rm. 2108, 20892, Bethesda, MD, USA aut JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/7(2015-10-01), 1081-1095 0949-8257 20:7<1081 2015 20 775 https://doi.org/10.1007/s00775-015-1290-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00775-015-1290-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Jagodinsky Justin Laboratory of Cell Biology, National Cancer Institute, Center for Cancer Research, National Institutes of Health, 37 Convent Drive, Rm. 2108, 20892, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Sulima Agnieszka Imaging Probe Development Center, National Institutes of Health, Rockville, MD, USA aut NATIONALLICENCE 700 1- Cao Yiqi Laboratory of Cell Biology, National Cancer Institute, Center for Cancer Research, National Institutes of Health, 37 Convent Drive, Rm. 2108, 20892, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Poprawski Joanna Laboratory of Cell Biology, National Cancer Institute, Center for Cancer Research, National Institutes of Health, 37 Convent Drive, Rm. 2108, 20892, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Blackman Burchelle Imaging Probe Development Center, National Institutes of Health, Rockville, MD, USA aut NATIONALLICENCE 700 1- Lloyd John Advanced Mass Spectrometry Facility, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 20892, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Swenson Rolf Imaging Probe Development Center, National Institutes of Health, Rockville, MD, USA aut NATIONALLICENCE 700 1- Gottesman Michael Laboratory of Cell Biology, National Cancer Institute, Center for Cancer Research, National Institutes of Health, 37 Convent Drive, Rm. 2108, 20892, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Hall Matthew Laboratory of Cell Biology, National Cancer Institute, Center for Cancer Research, National Institutes of Health, 37 Convent Drive, Rm. 2108, 20892, Bethesda, MD, USA aut NATIONALLICENCE 773 0- JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/7(2015-10-01), 1081-1095 0949-8257 20:7<1081 2015 20 775