Biological properties of novel ruthenium- and osmium-nitrosyl complexes with azole heterocycles

Handle URI:
http://hdl.handle.net/10754/601317
Title:
Biological properties of novel ruthenium- and osmium-nitrosyl complexes with azole heterocycles
Authors:
Novak, Maria S.; Büchel, Gabriel E. ( 0000-0002-5055-7099 ) ; Keppler, Bernhard K.; Jakupec, Michael A.
Abstract:
Since the discovery that nitric oxide (NO) is a physiologically relevant molecule, there has been great interest in the use of metal nitrosyl compounds as antitumor pharmaceuticals. Particularly interesting are those complexes which can deliver NO to biological targets. Ruthenium- and osmium-based compounds offer lower toxicity compared to other metals and show different mechanisms of action as well as different spectra of activity compared to platinum-based drugs. Novel ruthenium- and osmium-nitrosyl complexes with azole heterocycles were studied to elucidate their cytotoxicity and possible interactions with DNA. Apoptosis induction, changes of mitochondrial transmembrane potential and possible formation of reactive oxygen species were investigated as indicators of NO-mediated damage by flow cytometry. Results suggest that ruthenium- and osmium-nitrosyl complexes with the general formula (indazolium)[cis/trans-MCl4(NO)(1H-indazole)] have pronounced cytotoxic potency in cancer cell lines. Especially the more potent ruthenium complexes strongly induce apoptosis associated with depolarization of mitochondrial membranes, and elevated reactive oxygen species levels. Furthermore, a slight yet not unequivocal trend to accumulation of intracellular cyclic guanosine monophosphate attributable to NO-mediated effects was observed.
KAUST Department:
Physical Sciences and Engineering (PSE) Division; KAUST Catalysis Center (KCC)
Citation:
Biological properties of novel ruthenium- and osmium-nitrosyl complexes with azole heterocycles 2016 JBIC Journal of Biological Inorganic Chemistry
Publisher:
Springer Science + Business Media
Journal:
JBIC Journal of Biological Inorganic Chemistry
Issue Date:
9-Mar-2016
DOI:
10.1007/s00775-016-1345-z
Type:
Article
ISSN:
0949-8257; 1432-1327
Sponsors:
Austrian Science Fund (FWF). We are deeply grateful to Prof. Dr. Vladimir Arion for overall support and collaborations. Authors wish to thank Anatolie Gavriluta (Université Claude Bernard Lyon 1, France) for cooperation. This work was performed as part of an Austrian-French joint project supported in France by ANR (Agence Nationale de la Recherche) through the project VILYGRu (No. ANR-09-BLAN-0420-01) and in Austria by the Austrian Science Fund (FWF) through the project I374-N19. Partial support by the Austrian Science Fund through the project P-22339-N19 is also acknowledged.
Additional Links:
http://link.springer.com/10.1007/s00775-016-1345-z
Appears in Collections:
Articles; Physical Sciences and Engineering (PSE) Division; KAUST Catalysis Center (KCC)

Full metadata record

DC FieldValue Language
dc.contributor.authorNovak, Maria S.en
dc.contributor.authorBüchel, Gabriel E.en
dc.contributor.authorKeppler, Bernhard K.en
dc.contributor.authorJakupec, Michael A.en
dc.date.accessioned2016-03-13T13:52:45Zen
dc.date.available2016-03-13T13:52:45Zen
dc.date.issued2016-03-09en
dc.identifier.citationBiological properties of novel ruthenium- and osmium-nitrosyl complexes with azole heterocycles 2016 JBIC Journal of Biological Inorganic Chemistryen
dc.identifier.issn0949-8257en
dc.identifier.issn1432-1327en
dc.identifier.doi10.1007/s00775-016-1345-zen
dc.identifier.urihttp://hdl.handle.net/10754/601317en
dc.description.abstractSince the discovery that nitric oxide (NO) is a physiologically relevant molecule, there has been great interest in the use of metal nitrosyl compounds as antitumor pharmaceuticals. Particularly interesting are those complexes which can deliver NO to biological targets. Ruthenium- and osmium-based compounds offer lower toxicity compared to other metals and show different mechanisms of action as well as different spectra of activity compared to platinum-based drugs. Novel ruthenium- and osmium-nitrosyl complexes with azole heterocycles were studied to elucidate their cytotoxicity and possible interactions with DNA. Apoptosis induction, changes of mitochondrial transmembrane potential and possible formation of reactive oxygen species were investigated as indicators of NO-mediated damage by flow cytometry. Results suggest that ruthenium- and osmium-nitrosyl complexes with the general formula (indazolium)[cis/trans-MCl4(NO)(1H-indazole)] have pronounced cytotoxic potency in cancer cell lines. Especially the more potent ruthenium complexes strongly induce apoptosis associated with depolarization of mitochondrial membranes, and elevated reactive oxygen species levels. Furthermore, a slight yet not unequivocal trend to accumulation of intracellular cyclic guanosine monophosphate attributable to NO-mediated effects was observed.en
dc.description.sponsorshipAustrian Science Fund (FWF). We are deeply grateful to Prof. Dr. Vladimir Arion for overall support and collaborations. Authors wish to thank Anatolie Gavriluta (Université Claude Bernard Lyon 1, France) for cooperation. This work was performed as part of an Austrian-French joint project supported in France by ANR (Agence Nationale de la Recherche) through the project VILYGRu (No. ANR-09-BLAN-0420-01) and in Austria by the Austrian Science Fund (FWF) through the project I374-N19. Partial support by the Austrian Science Fund through the project P-22339-N19 is also acknowledged.en
dc.language.isoenen
dc.publisherSpringer Science + Business Mediaen
dc.relation.urlhttp://link.springer.com/10.1007/s00775-016-1345-zen
dc.rightsThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons. org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.en
dc.subjectRutheniumen
dc.subjectNitrosyl complexesen
dc.subjectCanceren
dc.subjectApoptosisen
dc.subjectcGMP levelen
dc.titleBiological properties of novel ruthenium- and osmium-nitrosyl complexes with azole heterocyclesen
dc.typeArticleen
dc.contributor.departmentPhysical Sciences and Engineering (PSE) Divisionen
dc.contributor.departmentKAUST Catalysis Center (KCC)en
dc.identifier.journalJBIC Journal of Biological Inorganic Chemistryen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionInstitute of Inorganic Chemistry, University of Vienna, 1090, Vienna, Austriaen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorBüchel, Gabriel E.en
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