Abstract
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.
Highlights
The increasing consumption of sugar on our daily diet has posed diabetes as a world-wide first-line problem of which society is becoming conscious
This model has been used extensively to study various diseases, including diabetes, an endocrine dysfunction resulting from insulin deficiency or incapability of peripheral tissues to respond to insulin [42]
All products assayed present anti-inflammatory effects at the concentrations used, being able to revert the 100% cell cycle arrest in the G0/G1 phase induced by LPS in RAW 264.7 murine monocyte/macrophage cells, no significant differences were found in the cell cycle effects for the different products assayed
Summary
The increasing consumption of sugar on our daily diet has posed diabetes as a world-wide first-line problem of which society is becoming conscious. There is a growing interest of the scientific community in the development of new drugs that improve diabetes treatment efficacy showing minor adverse reactions and using different administration routes. Recent studies aim to develop new drugs that can be administered orally for the treatment of diabetes [2,3]. Coordination compounds have demonstrated to inhibit enzymes that play a major role in modulating insulin sensitivity [4,5]. The design of these novel materials based on metal ions could be an excellent tool to improve the distribution and, the effectiveness of metals as oral anti-diabetic agents in the treatment of diabetes mellitus, giving an alternative to traditional insulin therapy
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