Bis(dipyridophenazine)(2‐(2′‐pyridyl)pyrimidine‐4‐carboxylic acid)ruthenium(II) Hexafluorophosphate: A Lesson in Stubbornness. Issue 7 (3rd March 2014)

• Record Type: Journal Article
• Authors: Joshi, Tanmaya; Pierroz, Vanessa; Ferrari, Stefano; Gasser, Gilles
• Is Part Of: ChemMedChem. Volume 9:Issue 7(2014:Jul.)
• Page Start: 1419
• Page End: 1427
• Publication Date: 2014-03-03
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201400029
• Languages: English
• ISSNs: 1860-7179

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Ruthenium complexes are currently considered to be among the most promising alternatives to platinum anticancer drugs. In this work, thirteen structural analogues and organelle/receptor‐targeting peptide bioconjugates of a cytotoxic bis(dppz)‐Ru^II complex [Ru(dppz)₂(CppH)](PF₆)₂ (<bold>1</bold>) were prepared, characterized, and assessed for their cytotoxicity and cellular localization (CppH=2‐(2′‐pyridyl)pyrimidine‐4‐carboxylic acid; dppz=dipyrido[3, 2‐<italic>a</italic>:2′, 3′‐<italic>c</italic>]phenazine). It was observed that structural modifications (lipophilicity, charge, and size‐based) result in the cytotoxic potency of <bold>1</bold> being compromised. Confocal microscopy studies revealed that unlike <bold>1</bold>, the screened complexes/bioconjugates do not have a preferential accumulation in mitochondria. The results of this important structure–activity relationship strongly support our initial hypothesis that accumulation in mitochondria is crucial for <bold>1</bold> to exert its cytotoxic action.</p> </abstract>