A Bis(dipyridophenazine)(2‐(2‐pyridyl)pyrimidine‐4‐carboxylic acid)ruthenium(II) Complex with Anticancer Action upon Photodeprotection1. Issue 11 (5th February 2014)

• Record Type: Journal Article
• Authors: Joshi, Tanmaya; Pierroz, Vanessa; Mari, Cristina; Gemperle, Lea; Ferrari, Stefano; Gasser, Gilles
• Is Part Of: Angewandte Chemie international edition. Volume 53:Issue 11(2014)
• Page Start: 2960
• Page End: 2963
• Publication Date: 2014-02-05
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201309576
• Languages: English
• ISSNs: 1433-7851

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Improving the selectivity of anticancer drugs towards cancer cells is one of the main goals of drug optimization; the prodrug strategy has been one of the most promising. A light‐triggered prodrug strategy is presented as an efficient approach for controlling cytotoxicity of the substitutionally inert cytotoxic complex [Ru(dppz)₂(CppH)](PF₆)₂ (<bold>C1</bold>; CppH=2‐(2‐pyridyl)pyrimidine‐4‐carboxylic acid; dppz=dipyrido[3, 2‐<italic>a</italic>:2′, 3′‐c]phenazine). Attachment of a photolabile 3‐(4, 5‐dimethoxy‐2‐nitrophenyl)‐2‐butyl (DMNPB) ester ("photocaging") makes the otherwise active complex <bold>C1</bold> innocuous to both cancerous (HeLa and U2OS) and non‐cancerous (MRC‐5) cells. The cytotoxic action can be successfully unleashed in living cells upon light illumination (350 nm), reaching similar level of activity as the parent cytotoxic compound <bold>C1</bold>. This is the first substitutionally inert cytotoxic metal complex to be used as a light‐triggered prodrug candidate.</p> </abstract>