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

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.

Revealing the Angiopathy of Lacrimal Gland Lesion in Type 2 Diabetes

“…It was reported that the therapy of an ophthalmic in situ gel formulation incorporating disulfiram (DIS) nanoparticles (Dis-NPs/ISG) might contribute to restore retinal dysfunction in diabetic retinopathy (DR), a diabetic vascular lesion (Deguchi et al, 2020 ). Bumetanide also has been demonstrated to play an important role in antidiabetic activity with low in vitro cell toxicity through antiinflammatory effects (Navas et al, 2020 ) and can reduce diabetic vascular dysfunction by suppression of angiogenesis (Topper et al, 1997 ; Guzel et al, 2020 ). Ambroxol can significantly inhibit proinflammatory cytokines, reduce lung inflammation, and accelerate recovery by reducing vascular permeability in acute lung injury (Su et al, 2004 ).…”

Diclofenac N-Derivatives as Therapeutic Agents with Anti-Inflammatory and Anti-Cancer Effect

“…Nitric oxide (NO), a molecule mediator in acute or chronic inflammation, is produced by constitutive or inducible nitric oxide synthases (iNOS). Its production is activated in response to pro-inflammatory signals as cytokines such as TNFα (tumor necrosis factor α) or INF-γ (interferon-γ), enterotoxin, or LPS (either bacterial lipopolysaccharide), in macrophages [ 44 ]. Here, the decrease of NO concentration has been used as an indirect marker of the inflammatory process [ 44 , 45 ].…”

“…Its production is activated in response to pro-inflammatory signals as cytokines such as TNFα (tumor necrosis factor α) or INF-γ (interferon-γ), enterotoxin, or LPS (either bacterial lipopolysaccharide), in macrophages [44]. Here, the decrease of NO concentration has been used as an indirect marker of the inflammatory process [44,45]. In the inflammatory response process, NO is released as an intermediate or second messenger.…”

The combination of ciprofloxacin and indomethacin suppresses the level of inflammatory cytokines secreted by macrophages in vitro

“…Moreover, Navas et al. 38 also showed that indomethacin conferred no cytotoxicity on cell viability in vitro .…”