Bis(dipyridophenazine)(2‐(2′‐pyridyl)pyrimidine‐4‐carboxylic acid)ruthenium(II) Hexafluorophosphate: A Lesson in Stubbornness |
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| Authors: | Dr. Tanmaya Joshi Vanessa Pierroz Priv.‐Doz. Dr. Stefano Ferrari Prof. Dr. Gilles Gasser |
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| Affiliation: | 1. Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland) http://www.gassergroup.com;2. Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland) |
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| Abstract: | 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)‐RuII complex [Ru(dppz)2(CppH)](PF6)2 ( 1 ) were prepared, characterized, and assessed for their cytotoxicity and cellular localization (CppH=2‐(2′‐pyridyl)pyrimidine‐4‐carboxylic acid; dppz=dipyrido[3,2‐a:2′,3′‐c]phenazine). It was observed that structural modifications (lipophilicity, charge, and size‐based) result in the cytotoxic potency of 1 being compromised. Confocal microscopy studies revealed that unlike 1 , 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 1 to exert its cytotoxic action. |
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| Keywords: | anticancer agents bioinorganic chemistry cytotoxicity ruthenium polypyridyl complexes structure– activity relationships |
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