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Designing Single-Molecule Magnets as Drugs with Dual Anti-Inflammatory and Anti-Diabetic Effects

We have designed and synthesized two novel cobalt coordination compounds using bumetanide (bum) and indomethacin (ind) therapeutic agents. The anti-inflammatory effects of cobalt metal complexes with ind and bum were assayed in lipopolysaccharide stimulated RAW 264.7 macrophages by inhibition of nit...

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Autores principales: Navas, Arturo, Jannus, Fatin, Fernández, Belén, Cepeda, Javier, Medina O’Donnell, Marta, Díaz-Ruiz, Luis, Sánchez-González, Cristina, Llopis, Juan, Seco, José M., Rufino-Palomares, E., Lupiáñez, José Antonio, Gómez-Ruiz, Santiago, Quiles, José Luis, Battino, Maurizio, Choquesillo-Lazarte, Duane, Ruiz-Muelle, Ana Belén, Fernández, Ignacio, Reyes-Zurita, Fernando, Rodríguez-Diéguez, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246571/
https://www.ncbi.nlm.nih.gov/pubmed/32365648
http://dx.doi.org/10.3390/ijms21093146
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author Navas, Arturo
Jannus, Fatin
Fernández, Belén
Cepeda, Javier
Medina O’Donnell, Marta
Díaz-Ruiz, Luis
Sánchez-González, Cristina
Llopis, Juan
Seco, José M.
Rufino-Palomares, E.
Lupiáñez, José Antonio
Gómez-Ruiz, Santiago
Quiles, José Luis
Battino, Maurizio
Choquesillo-Lazarte, Duane
Ruiz-Muelle, Ana Belén
Fernández, Ignacio
Reyes-Zurita, Fernando
Rodríguez-Diéguez, Antonio
author_facet Navas, Arturo
Jannus, Fatin
Fernández, Belén
Cepeda, Javier
Medina O’Donnell, Marta
Díaz-Ruiz, Luis
Sánchez-González, Cristina
Llopis, Juan
Seco, José M.
Rufino-Palomares, E.
Lupiáñez, José Antonio
Gómez-Ruiz, Santiago
Quiles, José Luis
Battino, Maurizio
Choquesillo-Lazarte, Duane
Ruiz-Muelle, Ana Belén
Fernández, Ignacio
Reyes-Zurita, Fernando
Rodríguez-Diéguez, Antonio
author_sort Navas, Arturo
collection PubMed
description We have designed and synthesized two novel cobalt coordination compounds using bumetanide (bum) and indomethacin (ind) therapeutic agents. The anti-inflammatory effects of cobalt metal complexes with ind and bum were assayed in lipopolysaccharide stimulated RAW 264.7 macrophages by inhibition of nitric oxide production. Firstly, we determined the cytotoxicity and the anti-inflammatory potential of the cobalt compounds and ind and bum ligands in RAW 264.7 cells. Indomethacin-based metal complex was able to inhibit the NO production up to 35% in a concentration-dependent manner without showing cytotoxicity, showing around 6–37 times more effective than indomethacin. Cell cycle analysis showed that the inhibition of NO production was accompanied by a reversion of the differentiation processes in LPS-stimulated RAW 264.7 cells, due to a decreased of cell percentage in G0/G1 phase, with the corresponding increase in the number of cells in S phase. These two materials have mononuclear structures and show slow relaxation of magnetization. Moreover, both compounds show anti-diabetic activity with low in vitro cell toxicities. The formation of metal complexes with bioactive ligands is a new and promising strategy to find new compounds with high and enhanced biochemical properties and promises to be a field of great interest.
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spelling pubmed-72465712020-06-10 Designing Single-Molecule Magnets as Drugs with Dual Anti-Inflammatory and Anti-Diabetic Effects Navas, Arturo Jannus, Fatin Fernández, Belén Cepeda, Javier Medina O’Donnell, Marta Díaz-Ruiz, Luis Sánchez-González, Cristina Llopis, Juan Seco, José M. Rufino-Palomares, E. Lupiáñez, José Antonio Gómez-Ruiz, Santiago Quiles, José Luis Battino, Maurizio Choquesillo-Lazarte, Duane Ruiz-Muelle, Ana Belén Fernández, Ignacio Reyes-Zurita, Fernando Rodríguez-Diéguez, Antonio Int J Mol Sci Article We have designed and synthesized two novel cobalt coordination compounds using bumetanide (bum) and indomethacin (ind) therapeutic agents. The anti-inflammatory effects of cobalt metal complexes with ind and bum were assayed in lipopolysaccharide stimulated RAW 264.7 macrophages by inhibition of nitric oxide production. Firstly, we determined the cytotoxicity and the anti-inflammatory potential of the cobalt compounds and ind and bum ligands in RAW 264.7 cells. Indomethacin-based metal complex was able to inhibit the NO production up to 35% in a concentration-dependent manner without showing cytotoxicity, showing around 6–37 times more effective than indomethacin. Cell cycle analysis showed that the inhibition of NO production was accompanied by a reversion of the differentiation processes in LPS-stimulated RAW 264.7 cells, due to a decreased of cell percentage in G0/G1 phase, with the corresponding increase in the number of cells in S phase. These two materials have mononuclear structures and show slow relaxation of magnetization. Moreover, both compounds show anti-diabetic activity with low in vitro cell toxicities. The formation of metal complexes with bioactive ligands is a new and promising strategy to find new compounds with high and enhanced biochemical properties and promises to be a field of great interest. MDPI 2020-04-29 /pmc/articles/PMC7246571/ /pubmed/32365648 http://dx.doi.org/10.3390/ijms21093146 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Navas, Arturo
Jannus, Fatin
Fernández, Belén
Cepeda, Javier
Medina O’Donnell, Marta
Díaz-Ruiz, Luis
Sánchez-González, Cristina
Llopis, Juan
Seco, José M.
Rufino-Palomares, E.
Lupiáñez, José Antonio
Gómez-Ruiz, Santiago
Quiles, José Luis
Battino, Maurizio
Choquesillo-Lazarte, Duane
Ruiz-Muelle, Ana Belén
Fernández, Ignacio
Reyes-Zurita, Fernando
Rodríguez-Diéguez, Antonio
Designing Single-Molecule Magnets as Drugs with Dual Anti-Inflammatory and Anti-Diabetic Effects
title Designing Single-Molecule Magnets as Drugs with Dual Anti-Inflammatory and Anti-Diabetic Effects
title_full Designing Single-Molecule Magnets as Drugs with Dual Anti-Inflammatory and Anti-Diabetic Effects
title_fullStr Designing Single-Molecule Magnets as Drugs with Dual Anti-Inflammatory and Anti-Diabetic Effects
title_full_unstemmed Designing Single-Molecule Magnets as Drugs with Dual Anti-Inflammatory and Anti-Diabetic Effects
title_short Designing Single-Molecule Magnets as Drugs with Dual Anti-Inflammatory and Anti-Diabetic Effects
title_sort designing single-molecule magnets as drugs with dual anti-inflammatory and anti-diabetic effects
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246571/
https://www.ncbi.nlm.nih.gov/pubmed/32365648
http://dx.doi.org/10.3390/ijms21093146
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