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

Autor: Navas A; Department of Inorganic Chemistry, C/ Severo Ochoa s/n, University of Granada, 18071 Granada, Spain., Jannus F; Department of Biochemistry and Molecular Biology I, Severo Ochoa s/n, University of Granada, 18071 Granada, Spain., Fernández B; Institute of Parasitology and Biomedicine 'López-Neyra', CSIC, Av. Conocimiento s/n, 18600 Granada, Spain., Cepeda J; Department of Applied Chemistry, University of The Basque Country (UPV/EHU), 20018 San Sebastián, Spain., Medina O'Donnell M; Department of Organic Chemistry, C/ Severo Ochoa s/n, University of Granada, 18071 Granada, Spain., Díaz-Ruiz L; Department of Biochemistry and Molecular Biology I, Severo Ochoa s/n, University of Granada, 18071 Granada, Spain., Sánchez-González C; Department of Physiology, University Campus of Cartuja, University of Granada, 18071 Granada, Spain., Llopis J; Department of Physiology, University Campus of Cartuja, University of Granada, 18071 Granada, Spain., Seco JM; Department of Applied Chemistry, University of The Basque Country (UPV/EHU), 20018 San Sebastián, Spain., Rufino-Palomares E; Department of Biochemistry and Molecular Biology I, Severo Ochoa s/n, University of Granada, 18071 Granada, Spain., Lupiáñez JA; Department of Biochemistry and Molecular Biology I, Severo Ochoa s/n, University of Granada, 18071 Granada, Spain., Gómez-Ruiz S; Department of Biology and Geology, Physics and Inorganic Chemistry, Rey Juan Carlos University, Calle Tulipán s/n, 28933 Móstoles (Madrid), Spain., Quiles JL; Department of Physiology. Institute of Nutrition and Food Technology 'Jose Mataix', Biomedical Research Center, Avda. Conocimiento s/n, 18100 Armilla, Spain., Battino M; Department of Clinical Specialist and Odontostomatological Sciences (DISCO) -Sez. Biochemistry, Faculty of Medicine, Polytechnic University of Marche, 60131 Ancona, Italy., Choquesillo-Lazarte D; Laboratorio de Estudios Cristalográficos, IACT (CSIC-UGR), Avda. de las Palmeras 4, 18100 Armilla, Spain., Ruiz-Muelle AB; Department of Chemistry and Physics, Research Centre CIAIMBITAL, University of Almería, Ctra. Sacramento s/n, 04120 Almería, Spain., Fernández I; Department of Chemistry and Physics, Research Centre CIAIMBITAL, University of Almería, Ctra. Sacramento s/n, 04120 Almería, Spain., Reyes-Zurita F; Department of Biochemistry and Molecular Biology I, Severo Ochoa s/n, University of Granada, 18071 Granada, Spain., Rodríguez-Diéguez A; Department of Inorganic Chemistry, C/ Severo Ochoa s/n, University of Granada, 18071 Granada, Spain.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2020 Apr 29; Vol. 21 (9). Date of Electronic Publication: 2020 Apr 29.
DOI: 10.3390/ijms21093146
Abstrakt: 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.
Databáze: MEDLINE
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