Evaluation of fluorophore-tethered platinum complexes to monitor the fate of cisplatin analogs

Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry
Justin C JagodinskyMatthew D Hall

Abstract

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.

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Citations

Jun 9, 2016·Advanced Drug Delivery Reviews·Miles A Miller, Ralph Weissleder
Feb 15, 2017·Journal of Medicinal Chemistry·Dorian M Cheff, Matthew D Hall
Nov 23, 2017·Nature Communications·Andrew M BreglioLisa L Cunningham
Jan 14, 2020·The Cochrane Database of Systematic Reviews·Vitor F VasconcellosRachel Riera
Oct 19, 2017·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Ganna V KalaydaSabrina Gollos
Sep 25, 2018·Journal of Inorganic Biochemistry·Rachael M CunninghamVictoria J DeRose

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