Functional Mimics of Superoxide Dismutase Enzymes as Therapeutic Agents

Only one of a wide assortment of manganese-containing SOD mimicking compounds rescues the slow aerobic growth phenotypes of both Escherichia coli and Saccharomyces cerevisiae strains lacking superoxide dismutase enzymes

“…The SOD mimic from Metaphore, M40403, is reported to have SOD but not catalase activity in vitro, and it is quite stable chemically and highly unlikely to dissociate manganese ions under the conditions of our experiments [22][23][24]. The structurally similar but SOD-inactive compound, M40404, provided a useful control.…”

“…They are reported to react specifically with superoxide and not with other ROS or reactive nitrogen species [23,24]. The SOD-active compound, M40403 (see Scheme 1) was shown to be effective in a variety of model systems, such as ischemia-reperfusion injury in rat heart [25] and inflammation in rat [26,27].…”

Crystal structure of dinitrato-κO-bis(tris((1H-benzo[d]imidazol-2-yl)methyl)amine-κ4 N,N′,N′′,N′′′)-(μ2-cyclohexane-1,4-dicarboxylato-κ4 O,O′:O′′,O′′′)dimanganese(II) – methanol – water (1/6/2), C62H80Mn2N16O18

“…Mn-SOD is found in eukaryotic cell, prokaryotic cell and stroma of mitochondria. It has been proven by X-ray crystallography that the manganese in the Mn-SODs from Bacillus stearothermophilus [5], Thermus thermophilus [6] and humans [7] is five-coordinated in a trigonalbipyramidal geometry with a N 3 O 2 coordination sphere and is ligated by three histidine residues, one aspartic acid residue and a water molecule [8].…”

Nickel(ii) Complexes With ‘Non Innocent’ Ligands – Cycloaminomethyl Derivatives of 1,2-Dihydroxybenzene: Sod-Like and Antimicrobial Activity

“…Many of the limiting factors could be overcome by developing synthetic, low-molecular-weight mimics of the SOD enzyme and by using a direct method to measure the SOD-like activity of these complexes [9]. It was found that Ni-containing low-molecular analogues of Ni-SOD can interfere in the inactivation mechanism of active oxygen forms of fungi and some bacteria and exhibit antimicrobial activity through competition with the native SOD [10]. Thus there are facts suggesting that redox-active metal complexes with antioxidants as ligands possess antimicrobial activity together with the SOD-like one.…”