superoxide dismutase

Superoxide dismutase (SOD), an exclusive antioxidant enzyme, catalyzes the dismutation of the superoxide anion into oxygen and hydrogen peroxide, averting peroxynitrite formation and subsequent harm. It is extensively studied and utilized in various applications, including anti-inflammatory, antitumor, radiation protection, and antisenility [1].

EUK-134, a synthetic superoxide dismutase (SOD) catalase mimetic, exhibits potent antioxidant activities and inhibits the formation of β-amyloid and related amyloid fibrils.

TriacetonaMine (Vincubine) protects the activitis of superoxide dismutase(SOD) and creatine phos-phate kinase (CPK); it also inhibits CaCl2 induced agglomeration of thromocyte. Triacetonamine can improve the constructile function of heart mus-cles of acute anemia and decrease the content of malodialdehyde (MDA) in the heart muscles.

BNTA is a potent extracellular matrix (ECM) modulator. In a rat model of arthritis, BNTA modulates arthritis by promoting the synthesis of cartilage structural molecules on chondrocytes through the induction of superoxide dismutase 3 (SOD3) and regulating chondrogenesis through superoxide anion elimination.

ATN-224 (Bis(choline)tetrathiomolybdate) inhibits SOD1 activity in endothelial cells, an effect that is dose dependent with an IC50 of 17.5±3.7 nM. ATN-224 is an oral Cu2+/Zn2+-superoxide dismutase 1 (SOD1) inhibitor.

Mito-TEMPO, a mitochondria-targeted superoxide dismutase mimetic, scavenges superoxide and alkyl radicals, preventing mitochondrial oxidation, necrosis, and apoptosis.

MitoTEMPOL is a mitochondria-targeting superoxide dismutase mimetic that reduces mitochondrial O2- to H2O2. Like the related compound MitoTEMPO , MitoTEMPOL combines an antioxidant moiety (here, TEMPOL, also known as 4-hydroxy-TEMPO) with the lipophilic cation triphenylphosphonium, which allows it to pass through lipid bilayers and accumulate in mitochondria. MitoTEMPOL has been used to elucidate the role of mitochondria-derived superoxide in mitochondrial, cellular, and whole animal signaling.

Taraxerone has allelopathic and antifungal effects.Taraxerone prevents catalase, superoxide dismutase, and reduces glutathione concentrations from the decrease induced by ethanol administration with the concentration dependent manner.

MTP 131 is a mitochondria-targeted peptide antioxidant.1,2It localizes to the mitochondria and reducestert-butyl hydroperoxide-induced lipid peroxidation and apoptosis in SH-SY5Y cells when used at concentrations ranging from 0.001 to 1 nM.1MTP 131 (2 mg kg) reduces infarct volume, hemispheric swelling, and glutathione (GSH) depletion in a mouse model of acute cerebral ischemia induced by middle cerebral artery occlusion (MCAO).2It increases survival, improves motor function, and decreases degeneration of the lumbar spinal cord in a superoxide dismutase 1 mutant (SOD1G93A) transgenic mouse model of amyotrophic lateral sclerosis (ALS) when administered at a dose of 5 mg kg. MTP 131 reduces albuminuria, urinary hydrogen peroxide levels, and mesangial matrix accumulation, as well as preserves superoxide production, in adb dbmouse model of diabetic nephropathy.3 1.Zhao, K., Luo, G., Giannelli, S., et al.Mitochondria-targeted peptide prevents mitochondrial depolarization and apoptosis induced by tert-butyl hydroperoxide in neuronal cell linesBiochem. Pharmacol.70(12)1796-1806(2005) 2.Szeto, H.H.Mitochondria-targeted peptide antioxidants: Novel neuroprotective agentsAAPS J.8(3)E521-E531(2006) 3.Miyamoto, S., Zhang, G., Hall, D., et al.Restoring mitochondrial superoxide levels with elamipretide (MTP-131) protects db db mice against progression of diabetic kidney diseaseJ. Biol. Chem.295(21)7249-7260(2020)

Deacetylasperulosidic Acid is a natural compound of Morinda citrifolia fruit. It has antioxidant activity by increasing superoxide dismutase activity. It also prevents 4-nitroquinoline 1-oxide (4NQO) induced DNA damage in vitro, suppresses IL-2 production along with the activation of natural killer cells.

CMB-087229 is an inhibitor of mutant superoxide dismutase 1 (SOD1) protein aggregation, exhibiting an IC50 of 67 nM, and holds potential for use in amyotrophic lateral sclerosis research [1].

19-epi-Scholaricine, an orally active indole alkaloid, downregulates collagen fibrosis expression and enhances superoxide dismutase (SOD) activities.

(E)-2-(2-Chlorostyryl)-3,5,6-trimethylpyrazine (CSTMP) is a stilbene derivative with antioxidant and anticancer activities. It stimulates proliferation of hydrogen peroxide-damaged ECV-304 cells (EC50 = 24.9 nM). CSTMP reduces hydrogen peroxide-induced release of lactate dehydrogenase (LDH) in and increases viability of human umbilical vein endothelial cells (HUVECs) in a concentration-dependent manner via inhibition of apoptosis. It reverses hydrogen peroxide-induced release of malondialdehyde (MDA) and decreases in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities as well as increases constitutive nitric oxide synthase (cNOS) activity and nitric oxide (NO) production in HUVECs. CSTMP also induces cell death of A549 non-small cell lung cancer (NSCLC) cells in an IRE1α-dependent manner through induction of IRE1α-TRAF2-ASK1 complex-mediated endoplasmic reticulum (ER) stress and mitochondrial apoptosis.

CLR01 is a molecular tweezer. CLR01 reduces aggregated, pathologic, and seeding-competent α-synuclein in experimental multiple system atrophy. CLR01 inhibits aberrant superoxide dismutase 1 (SOD1) self-assembly in vitro and in the G93A-SOD1 mouse model of ALS. CLR01 inhibits Ebola and Zika virus infection. CLR01 Stabilizes a Disordered Protein-Protein Interface. CLR01, Modulates Aggregation of the Mutant p53 DNA Binding Domain and Inhibits Its Toxicity.

SP-8203 is a reactive oxygen species inhibitor and superoxide dismutase stimulant.

Tiomolibdate diammonium (NSC-286644) is an inhibitor of superoxide dismutase 1 (SOD1) exerting antiangiogenic and antitumor activities. Tiomolibdate diammonium inhibits the activities of cuproenzymes, including SOD1 and COX.

Imisopasem manganese (M40403) is a manganese superoxide dismutase (MnSOD) non-peptidyl mimetic.

MnTBAP chloride (Mn(III)TBAP) is a cell-permeable superoxide dismutase (SOD) mimetic and peroxynitrite scavenger that reduces the doubling time of SOD-E. coli by a factor of 2. MnTBAP chloride exhibits anti-inflammatory effects through upregulation of BMPR-II and inhibition of NFκB signaling. mnTBAP chloride is a manganese porphyrin complex with antioxidant properties and has potential for use in the study of fibrotic responses in chronic kidney diseases (CKDs).

Tat-Gap 19, a peptide inhibitor of connexin43 (Cx43) hemichannels, is derived from the HIV-1 Tat protein transduction domain fused with a nine-amino acid sequence from Cx43 residues 128-136. This compound, at a concentration of 10 µM, effectively suppresses glutamate-induced ATP release in primary rat hepatocytes, indicating inhibition of Cx43 hemichannel activity. Furthermore, Tat-Gap 19 demonstrates therapeutic potential by significantly reducing infarct volume in a mouse cerebral ischemia-reperfusion injury model following middle cerebral artery occlusion (MCAO) at a dosage of 25 mg/kg. Moreover, its intraperitoneal administration at 1 mg/kg per day ameliorates fibrosis and decreases the area of hepatic stellate cells, the precursors to myofibroblasts, expressing α-smooth muscle actin (α-SMA), in a model of thioacetamide-induced liver damage. Additionally, it enhances superoxide dismutase (SOD) activity in hepatic cells from the treated mice, indicating its antioxidative benefits.

Adrenochrome (Adraxone) is a cytotoxic molecule that can be used to kill bacteria. Adrenochrome is an oxidized product of Epinephrine. Adrenochrome is a coronary systolic compound that acts on rat hearts and is associated with cardiotoxicity and can be used to determine superoxide dismutase activity. Adrenochrome is a potential psychotropic drug for the study of nervous system diseases.

The metallo-protein Cu/Zn-superoxide dismutase (SOD1) is a ubiquitous enzyme responsible for scavenging superoxide radicals. Mutations in SOD1, which alter its metal binding capacity and can result in protein misfolding and aggregation, have been linked to familial amyotrophic lateral sclerosis (ALS). Cu-ATSM is an orally bioavailable, blood-brain barrier permeable complex that has traditionally been used in cellular imaging experiments to selectively label hypoxic tissue via its susceptibility to reduction by oxygen-depleted mitochondria. More recently, Cu-ATSM has been reported to improve locomotor function and survival in a transgenic ALS mouse model by delivering copper specifically to cells in the spinal cords of mice producing misfolded SOD1 proteins. Copper chaperone for SOD (CCS) is presumed to utilize the copper from Cu-ATSM to prevent misfolding of the SOD1 protein.

Diallyl tetrasulfide is an organosulfur compound that has been found in A. sativum and has diverse biological activities, including antimicrobial, antioxidant, and anticancer properties.[1],[2],[3],[4] It is active against the bacteria S. aureus and methicillin-resistant S. aureus (MRSA; MICs = 0.5 and 2 mg/L, respectively), as well as the fungi C. albicans, C. krusei, C. glabrata, A. niger, A. flavus, and A. fumigatus (MICs = 0.5, 4, 2, 1, 2, and 4 mg/L, respectively).[1] It reduces cadmium-induced increases in hepatic levels of thiobarbituric acid reactive substances (TBARS) and increases cadmium-induced decreases in the hepatic activity of superoxide dismutase (SOD1), catalase, GST, and glucose-6-phosphate dehydrogenase (G6PDH) in rats when administered at a dose of 40 mg/kg.[2] Diallyl tetrasulfide is cytotoxic to MCF-7 breast cancer cells (IC50 = 92 μM) and reduces tumor growth in a BGC-823 mouse xenograft model when administered at doses of 20, 30, and 40 mg/kg for 32 days.[3],[4]

Avasopasem manganese is a drug candidate of superoxide dismutase mimetic.

Trilobatin (P-Phlorizin) has anti-oxidant effect, can increase superoxide dismutase (SOD) activity.Trilobatin has anti-inflammatory effect, it potentially inhibits the lipopolysaccharide (LPS)-induced inflammatory response by suppressing the NF-κB signaling pathway.Trilobatin shows a strong inhibitory activity against α-glucosidase and a moderate inhibitory activity against α-amylase for management of postprandial hyperglycemia with less side effect.

NF-κΒ activator 1 can activate the nf-kappa Β gene activator, EC50 of 0.9 microns. NF-κΒ is widely used in eukaryotic cells as a gene regulating cell proliferation and cell survival. NF-κΒ activator 1 induces superoxide dismutase (SOD) 2 1 mRNA expression.

Cupferron is a superoxide dismutase inhibitor.

(+)-Lyoniresinol 9'-O-glucoside ((+)-Lyoniresinol 3α-O-β-D-glucopyranoside) is a compound obtained from the root bark of Lycium barbarum, which possesses antimicrobial and antioxidant activity and superoxide dismutase-like activity, and can be used for the study of Gram-positive bacterial infections.

Manganese(salen) chloride (EUK-8) is a superoxide dismutase and catalase mimetic, serving as an antioxidant with oxyradical scavenging properties, and ameliorates acute lung injury in endotoxemic swine.

BMX-001 is a third-generation, cationic, lipophilic, manganese (Mn), and porphyrin-based mimetic of the human mitochondrial manganese superoxide dismutase (MnSOD). It also has antioxidant and potential chemoprotective activities.

SC 55858 is a superoxide dismutase mimetic.

Antioxidant agent-3 (Compound 14q), a potent antioxidant, exhibits strong scavenging activity against DPPH radicals and ABTS+ radicals with IC50 values of 26.58 μM and 30.31 μM, respectively. Additionally, it enhances levels of reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione (GSH), while diminishing lactate dehydrogenase (LDH) in H2O2-treated HepG2 cells [1].

TMV-IN-4 (Compound 3), a tobacco mosaic virus (TMV) inhibitor, effectively strengthens plant resistance and tolerance to TMV by binding with the TMV helicase. Furthermore, it boosts activities of peroxidase and superoxide dismutase, augmenting tobacco's resilience to TMV infection [1].

Spirotetramat is an insecticide that demonstrates efficacy against C. pyrinymphs in vitro (LC50= 6.51-12.53 mg AI/L) and achieves a 99.2% mortality rate in C. pyrinymphs within European pear (P. communis) fields 15 days post-application at a dosage of 27 g/hectare. Additionally, it reduces embryonic viability and nymph survival in O. insidiosus. Spirotetramat exhibits aquatic toxicity by altering protein levels in organisms, specifically by increasing glutathione peroxidase (GPX) and superoxide dismutase (SOD) levels, decreasing malondialdehyde (MDA) levels, and causing lethality in Chinese toad (B. gargarizans) tadpoles (LC50= 6.98 mg/L). Its formulations are utilized in agricultural insect control. Spirotetramat is marketed exclusively for research and analytical applications, formulated for controlled laboratory settings without the availability of bulk sizes.

MitoTEMPO is a mitochondria-targeted superoxide dismutase mimetic that possesses superoxide and alkyl radical scavenging properties.[1] This compound combines the antioxidant piperidine nitroxide TEMPO with the lipophilic cation triphenylphosphonium, which allows it to pass through lipid bilayers and accumulate in mitochondria. Mitochondrial targeting of superoxide scavenging via mitoTEMPO has been examined for potential therapeutic benefit to a variety of mitochondrial dysfunctions arising from excessive reactive oxygen species.[2][3][4]

1-Stearoyl-2-docosahexaenoyl-sn-glycero-3-PC is a phospholipid in biological membranes containing stearic acid and docosahexaenoic acid at the sn-1 and sn-2 positions, respectively. It has been used to study the organization and dynamics of lipid membranes. In the superoxide dismutase 1 mutant transgenic mouse model of amyotrophic lateral sclerosis (ALS) 1-Stearoyl-2-docosahexaenoyl-sn-glycero-3-PC levels decrease in the anterior horn of L5 in late stages of the disease.1-Stearoyl-2-docosahexaenoyl-sn-glycero-3-PC can be used to study biological membranes.

LCS-1, a superoxide dismutase 1 (SOD1) inhibitor, effectively inhibits the enzymatic activity of SOD1 with an IC50 value of 1.07 μM. Additionally, LCS-1 triggers both early and late-stage apoptosis in multiple myeloma (MM.1S) cells [1] [2] [3].

AEOL-10150 pentachloride is a metalloporphyrin catalytic antioxidant and superoxide dismutase mimetic that protects lungs from radiation-induced injury.

Tofersen (BIIB067) is an antisense oligonucleotide used to inhibit the synthesis of superoxide dismutase 1 (SOD1) protein by facilitating the degradation of SOD1 mRNA via an RNase H-dependent mechanism. This compound holds potential for amyotrophic lateral sclerosis (ALS) research.

Rucosopasem manganese (GC4711) is a potent and selective superoxide dismutase (SOD) mimetic that efficiently converts superoxide to hydrogen peroxide. Designed for research purposes, this compound shows promise in cancer-related studies.

GHK-Cu acetate, a complex of the tripeptide Gly-His-Lys and a copper(II) ion, exhibits wound healing and anti-inflammatory properties. It enhances fibroblast proliferation, collagen production, and the release of pro-matrix metalloproteinase-2 (MMP-2) and glycosaminoglycans (GAGs), while also increasing decorin expression in rat wound tissue. Furthermore, at a concentration of 10 µM, it reduces levels of reactive oxygen species (ROS), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in LPS-stimulated RAW 264.7 cells. Additionally, GHK-Cu at 10 µg/g mitigates LPS-induced reductions in lung superoxide dismutase (SOD) activity and glutathione (GSH) levels, decreases the accumulation of cells and total protein in bronchoalveolar lavage fluid (BALF), and thus, attenuates acute lung injury in mice.

Ochratoxin A-13C20is intended for use as an internal standard for the quantification of ochratoxin A by GC- or LC-MS. Ochratoxin A is a mycotoxin that has been found inAspergillusandPenicillium.1It increases lipid peroxide levels and the number of apoptotic cells, as well as reduces superoxide dismutase activity in rat kidney when administered at a dose of 120 μg/kg.2Topical application of ochratoxin A (80 μg/mouse) induces DNA damage, cell cycle arrest at the G0/G1phase, and apoptosis in mouse skin cells.1It also initiates tumor formation in a two-stage mouse skin tumorigenesis model. Ochratoxin A has been found as a contaminant in a variety of foods.3

Mn(III)TMPyP is a manganese-porphyrin which acts as a superoxide dismutase (SOD) mimetic and peroxynitrite decomposition catalyst. SOD mimetics described to date are unstable and are capable of catalyzing undesired side-reactions in addition to the dismutation of the superoxide radical (O2-). Mn(III)TMPyP is an SOD mimetic with increased stability to pH and hydrogen peroxide. The rate constant for superoxide dismutation and peroxynitrite decomposition are 3.9 x 107 M-1s-1 and ~2 x 106 M-1s-1, respectively. Mn(III)TMPyP protected and enhanced the growth of SOD E. coli with a doubling time of 60 minutes (as compared to 240 minutes of the control) at 25 µM.

NUCC-0000323 is a potent inhibitor of superoxide dismutase 1 (SOD1), effectively suppressing SOD1 expression. This compound has applications in amyotrophic lateral sclerosis (ALS) research.

Ochratoxin α, a less toxic photolytic and thermal degradation product of Ochratoxin A, is characterized by reduced toxicity.