Termination, stabilization, and recycling of free-radical by phenolic estrogen derived drugs

Structure represents the quinolic ring that can spontaneously convert to a phenolic ring found in the structure of estrogens. The phenol () can then scavenge free radicals () and resonance-stabilize them () until reduced (X). Reduction of phenoxy radicals () is an enzyme-mediated process that uses ascorbic acid, glutathione-dependent free radical reductase, and a newly discovered NADPH-mediated reductive aromatization. This illustration was loosely based on work of Prokai et al. [].<p><b>Copyright information:</b></p><p>Taken from "Estrogens and neuroprotection in retinal diseases"</p><p></p><p>Molecular Vision 2008;14():1480-1486.</p><p>Published online 11 Aug 2008</p><p>PMCID:PMC2507727.</p><p></p

Effects of E2, PPT, DPN, ZYC-26 and ZYC-23 on intracellular lipid peroxidation in BSO-treated FRDA fibroblasts.

<p>All steroid concentrations were 100 nM, DMSO concentration was 0.1% and BSO concentration was 1 mM. Depicted are mean ± SD for n = 8 per group. * indicated p<0.05 versus BSO alone-treated cells. 1.0 normalized 8-isoprostane control concentration = 6.23 pg/mL.</p

Proposed mechanism of 17β-Estradiol in BSO-treated FRDA fibroblasts.

<p>Proposed mechanism of 17β-Estradiol in BSO-treated FRDA fibroblasts.</p

Effects of E2, PPT, DPN, ZYC-26 and ZYC-23 on the activity of aconitase in BSO-treated FRDA fibroblasts.

<p>All steroid concentrations were 100 nM, DMSO concentration was 0.1% and BSO concentration was 1 mM. Depicted are mean ± SD for n = 8 per group. * indicated p<0.05 versus BSO alone-treated cells.</p

Effects of E2, PPT, DPN, ZYC-26 and ZYC-23 on the collapse of mitochondrial membrane in BSO-treated FRDA fibroblasts.

<p>All steroid concentrations were 100 nM, DMSO concentration was 0.1% and BSO concentration was 1 mM. Depicted are mean ± SD for n = 8 per group. * indicated p<0.05 versus BSO alone-treated cells.</p

Effects of E2 and ZYC-26 on mitochondrial function in BSO-treated FRDA fibroblasts.

<p>A.) Oxygen consumption rate (OCR; in pMoles/min) B.) Basal respiratory rate (in pMoles/min) C.) Maximal respiratory rate (in pMoles/min) All steroid concentrations were 100 nM, DMSO concentration was 0.1% and BSO concentration was 1 mM. Depicted are mean ± SD for n = 8 per group. * indicated p<0.05 versus BSO alone-treated cells.</p

Synthesis and Biological Evaluation of 17β-Alkoxyestra-1,3,5(10)-trienes as Potential Neuroprotectants Against Oxidative Stress

17β-O-Alkyl ethers (methyl, ethyl, propyl, butyl, hexyl, and octyl) of estradiol were obtained from 3-O-benzyl-17β-estradiol with sodium hydride/alkyl halide, followed by the removal of the O-benzyl protecting group via catalytic transfer hydrogenation. An increase compared to estradiol in the protection of neural (HT-22) cells against oxidative stress due to exposure of glutamate was furnished by higher (C-3 to C-8) alkyl ethers, while methyl and ethyl ethers decreased the neuroprotective effect significantly. Lipophilic (butyl and octyl) ethers blocking the phenolic hydroxyl (3-OH) of A-ring were inactive

Figure 3

<p>A.) Calcein AM imaging demonstrating cell viability between vehicle control and BSO treatment groups at 24, 36 and 48 hours. Scale bar = 200 µm. B.) Effects of E2, PPT, DPN, ZYC-26 and ZYC-23 on cell viability in BSO-treated FRDA fibroblasts. All steroid concentrations were 100 nM, DMSO concentration was 0.1% and BSO concentration was 1 mM. Depicted are mean ± SD for n = 8 per group. * indicated p<0.05 versus BSO alone-treated cells.</p

Structures of compounds assessed for protection against BSO toxicity in FRDA fibroblasts.

<p>Structures of compounds assessed for protection against BSO toxicity in FRDA fibroblasts.</p

An N‑Heterocyclic Amine Chelate Capable of Antioxidant Capacity and Amyloid Disaggregation

Alzheimer’s disease is a neurodegenerative disorder characterized by the development of intracellular neurofibrillary tangles, deposition of extracellular amyloid beta (Aβ) plaques, along with a disruption of transition metal ion homeostasis in conjunction with oxidative stress. Spectroscopic, transmission electron microscopy, and scanning electron microscopy imaging studies show that 1 (pyclen) is capable of both preventing and disrupting Cu2+ induced AB1–40 aggregation. The pyridine backbone of 1 engenders antioxidant capacity, as shown by cellular DCFH-DA (dichlorodihydrofluorescein diacetate) assay in comparison to other N-heterocyclic amines lacking this aromatic feature. Finally, 1 prevents cell death induced by oxidative stress as shown by the Calcein AM assay. The results are supported using density functional theory studies which show that the pyridine backbone is responsible for the antioxidant capacity observed