title: A bis(dipyridophenazine)(2-(2-pyridyl)pyrimidine-4-carboxylic acid)ruthenium(II) complex with anticancer action upon photodeprotection.
abstract: 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(C1; CppH=2-(2-pyridyl)pyrimidine-4-carboxylic acid; dppz=dipyrido[3,2-a:2',3'-c]phenazine). Attachment of a photolabile 3-(4,5-dimethoxy-2-nitrophenyl)-2-butyl (DMNPB) ester ("photocaging") makes the otherwise active complex C1 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 C1. This is the first substitutionally inert cytotoxic metal complex to be used as a light-triggered prodrug candidate.
authors: Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland) http://www.gassergroup.com. tanmaya.joshi3@uzh.ch.
authors: Tanmaya
authors: T
authors: Joshi
authors: Vanessa
authors: V
authors: Pierroz
authors: Cristina
authors: C
authors: Mari
authors: Lea
authors: L
authors: Gemperle
authors: Stefano
authors: S
authors: Ferrari
authors: Gilles
authors: G
authors: Gasser
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D010782:Photolysis; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D056831:Coordination Complexes; D011355:Prodrugs; D011743:Pyrimidines; C000592862:bis(dipyridophenazine)(2-(2-pyridyl)pyrimidine-4-carboxylic acid)ruthenium(II); D012428:Ruthenium; C030986:pyrimidine
keywords: medicinal inorganic chemistry; photolysis; prodrugs; ruthenium; substitutionally inert complexes