97973-01-8Relevant academic research and scientific papers
Evaluation of fluorophore-tethered platinum complexes to monitor the fate of cisplatin analogs
Jagodinsky, Justin C.,Sulima, Agnieszka,Cao, Yiqi,Poprawski, Joanna E.,Blackman, Burchelle N.,Lloyd, John R.,Swenson, Rolf E.,Gottesman, Michael M.,Hall, Matthew D.
, p. 1081 - 1095 (2015)
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.
