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Quinoline‐Conjugated Ruthenacarboranes: Toward Hybrid Drugs with a Dual Mode of Action

The role of autophagy in cancer is often complex, ranging from tumor‐promoting to ‐suppressing effects. In this study, two novel hybrid molecules were designed, containing a ruthenacarborane fragment conjugated with a known modulator of autophagy, namely a quinoline derivative. The complex closo‐[3‐...

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Autores principales: Gozzi, Marta, Murganic, Blagoje, Drača, Dijana, Popp, John, Coburger, Peter, Maksimović‐Ivanić, Danijela, Mijatović, Sanja, Hey‐Hawkins, Evamarie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6973020/
https://www.ncbi.nlm.nih.gov/pubmed/31675152
http://dx.doi.org/10.1002/cmdc.201900349
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author Gozzi, Marta
Murganic, Blagoje
Drača, Dijana
Popp, John
Coburger, Peter
Maksimović‐Ivanić, Danijela
Mijatović, Sanja
Hey‐Hawkins, Evamarie
author_facet Gozzi, Marta
Murganic, Blagoje
Drača, Dijana
Popp, John
Coburger, Peter
Maksimović‐Ivanić, Danijela
Mijatović, Sanja
Hey‐Hawkins, Evamarie
author_sort Gozzi, Marta
collection PubMed
description The role of autophagy in cancer is often complex, ranging from tumor‐promoting to ‐suppressing effects. In this study, two novel hybrid molecules were designed, containing a ruthenacarborane fragment conjugated with a known modulator of autophagy, namely a quinoline derivative. The complex closo‐[3‐(η (6)‐p‐cymene)‐1‐(quinolin‐8‐yl‐acetate)‐3,1,2‐RuC(2)B(9)H(10)] (4) showed a dual mode of action against the LN229 (human glioblastoma) cell line, where it inhibited tumor‐promoting autophagy, and strongly inhibited cell proliferation, de facto blocking cellular division. These results, together with the tendency to spontaneously form nanoparticles in aqueous solution, make complex 4 a very promising drug candidate for further studies in vivo, for the treatment of autophagy‐prone glioblastomas.
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spelling pubmed-69730202020-01-27 Quinoline‐Conjugated Ruthenacarboranes: Toward Hybrid Drugs with a Dual Mode of Action Gozzi, Marta Murganic, Blagoje Drača, Dijana Popp, John Coburger, Peter Maksimović‐Ivanić, Danijela Mijatović, Sanja Hey‐Hawkins, Evamarie ChemMedChem Full Papers The role of autophagy in cancer is often complex, ranging from tumor‐promoting to ‐suppressing effects. In this study, two novel hybrid molecules were designed, containing a ruthenacarborane fragment conjugated with a known modulator of autophagy, namely a quinoline derivative. The complex closo‐[3‐(η (6)‐p‐cymene)‐1‐(quinolin‐8‐yl‐acetate)‐3,1,2‐RuC(2)B(9)H(10)] (4) showed a dual mode of action against the LN229 (human glioblastoma) cell line, where it inhibited tumor‐promoting autophagy, and strongly inhibited cell proliferation, de facto blocking cellular division. These results, together with the tendency to spontaneously form nanoparticles in aqueous solution, make complex 4 a very promising drug candidate for further studies in vivo, for the treatment of autophagy‐prone glioblastomas. John Wiley and Sons Inc. 2019-11-19 2019-12-17 /pmc/articles/PMC6973020/ /pubmed/31675152 http://dx.doi.org/10.1002/cmdc.201900349 Text en ©2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Full Papers
Gozzi, Marta
Murganic, Blagoje
Drača, Dijana
Popp, John
Coburger, Peter
Maksimović‐Ivanić, Danijela
Mijatović, Sanja
Hey‐Hawkins, Evamarie
Quinoline‐Conjugated Ruthenacarboranes: Toward Hybrid Drugs with a Dual Mode of Action
title Quinoline‐Conjugated Ruthenacarboranes: Toward Hybrid Drugs with a Dual Mode of Action
title_full Quinoline‐Conjugated Ruthenacarboranes: Toward Hybrid Drugs with a Dual Mode of Action
title_fullStr Quinoline‐Conjugated Ruthenacarboranes: Toward Hybrid Drugs with a Dual Mode of Action
title_full_unstemmed Quinoline‐Conjugated Ruthenacarboranes: Toward Hybrid Drugs with a Dual Mode of Action
title_short Quinoline‐Conjugated Ruthenacarboranes: Toward Hybrid Drugs with a Dual Mode of Action
title_sort quinoline‐conjugated ruthenacarboranes: toward hybrid drugs with a dual mode of action
topic Full Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6973020/
https://www.ncbi.nlm.nih.gov/pubmed/31675152
http://dx.doi.org/10.1002/cmdc.201900349
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