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

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posted on 2021-05-28, 19:42 authored by Arturo Navas, Fatin JannusFatin Jannus, Belén Fernández, Javier Cepeda, Marta Medina O’Donnell, Luis Díaz-Ruiz, Cristina Sánchez-González, Juan Llopis, José M. Seco, E. Rufino-Palomares, José Antonio Lupiáñez, Santiago Gómez-Ruiz, José Luis Quiles, Maurizio Battino, Duane Choquesillo-Lazarte, Ana Belén Ruiz-Muelle, Ignacio Fernández, Fernando Reyes-Zurita, Antonio Rodríguez-Diéguez
In this work we have synthesized two novel cobalt coordination compounds employing bumetanide (bum) and indomethacin (ind) therapeutic products. The anti-inflammatory activities of cobalt metal complexes with ind and bum were analyzed in lipopolysaccharide induced RAW 264.7 macrophages by inhibition of nitric oxide production. Firstly, we studied 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 capable 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 study demonstrated 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 reduction of cell percentage in G0/G1 phase, with the corresponding increment in the number of cells in S phase. These two compounds have mononuclear structures and show slow relaxation of magnetization. Also, both compounds show anti-diabetic effect with low in vitro cell toxicities.

Funding

This work has been funded by Junta de Andalucía (FQM-394 and FQM-1484), the Spanish Ministry of Economy and Competitiveness (MCIU/AEI/FEDER, UE) (PGC2018-102052-A-C22, PGC2018-102052- B-C21, and PGC2018-102047-B-I00) and Red Guipuzcoana de Ciencia, Tecnología e Innovación (OF188/2017), University of the Basque Country (GIU 17/13).

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