Designing Single-Molecule Magnets as Drugs with Dual Anti-Inflammatory and Anti-Diabetic Effects
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AuthorNavas, Arturo; Jannus, Fatin; Fernández, Belén; Medina-O'Donnell, Marta; Díaz Ruiz, Luis; Sánchez González, Cristina; Llopis González, Juan; Rufino Palomares, Eva; Lupiáñez Cara, José Antonio; Quiles Morales, José Luis; Reyes Zurita, Fernando Jesús; Rodríguez Diéguez, Antonio
BumetadineIndomethacinCobaltCoordination compoundsSingle ion magnetInflammatoryDiabetes
Navas, A., Jannus, F., Fernández, B., Cepeda, J., Medina O’Donnell, M., Díaz-Ruiz, L., ... & Lupiáñez, J. A. (2020). Designing Single-Molecule Magnets as Drugs with Dual Anti-Inflammatory and Anti-Diabetic Effects. International Journal of Molecular Sciences, 21(9), 3146. [doi:10.3390/ijms21093146]
SponsorshipThis 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). The authors thank for technical and human support provided by SGIker of UPV/EHU and European funding (ERDF and ESF).
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.