Studies related to antitumor antibiotics. Part VIII. Cleavage of DNA by streptonigrin analogues and the relationship to antineoplastic activity

1976 ◽  
Vol 54 (5) ◽  
pp. 446-452 ◽  
Author(s):  
J. William Lown ◽  
Soo-Khoon Sim
Keyword(s):  
Dna Cleavage ◽  
Chemical Mechanism ◽  
Antineoplastic Activity ◽  
Free Radical Scavengers ◽  
Antitumor Antibiotic ◽  
Antitumor Antibiotics ◽  
Radical Scavengers ◽  
Superoxide Ion ◽  
Circular Dna ◽  
The Relationship

A group of substituted 5,8-quinolinequinones which exhibit antineoplastic activity and which are structurally related to the antitumor antibiotic streptonigrin induce single strand cleavage of PM2 covalently-closed circular-DNA (ccc-DNA) when reductively activated. The cleavage which is detected by an ethidium fluorescence assay is specifically enhanced by cuprous and ferrous ion and is selectively inhibited by superoxide dismutase (EC 1.15.1.1) and catalase (EC 1.11.1.6) and by free radical scavengers. Independent generation of the superoxide ion by xanthine – xanthine oxidase (EC 1.2.3.2) also cleaves PM2 DNA and therefore a chemical mechanism for the scission process induced by the streptonigrin analogues is formulated. A correlation between rate of PM2 ccc-DNA cleavage and inhibition of Walker carcinosarcoma 256 is observed.

Studies related to antitumor antibiotics. Part VII. Synthesis of streptonigrin analogues and their single strand scission of DNA

1976 ◽  
Vol 54 (16) ◽  
pp. 2563-2572 ◽  
Author(s):  
J. William Lown ◽  
Soo-Khoon Sim
Keyword(s):  
Antitumor Activity ◽  
Dna Cleavage ◽  
Single Strand ◽  
Antitumor Antibiotic ◽  
Antitumor Antibiotics ◽  
Substitution Pattern ◽  
Circular Dna ◽  
Strand Scission ◽  
Independent Synthesis ◽  
Selective Catalysis

The syntheses of a group of 2-(o-nitrophenyl)- and 2-(o-aminophenyl)-5,8-quinolinediones which are structurally related to the antitumor antibiotic streptonigrin are described. Ambiguities in the position of required nucleophilic displacements are resolved by independent synthesis. The rates of single strand cleavage of PM2 ccc-DNA (covalently-closed circular-DNA) induced by these compounds are compared, which correlates with antitumor activity. The 2-(o-nitrophenyl) derivatives give consistently more rapid DNA cleavage than the 2-(o-aminophenyl) compounds. The autoxidations of the dihydroxyquinolines are subject to selective catalysis by Cu2+ on. 2-(o-Aminophenyl)-7-amino-6-methoxy-5,6-quinolinedione which has a substitution pattern most closely resembling streptonigrin also closely parallels the rate of scission of DNA of the latter in the presence of NADPH.

scholarly journals Background level of 8-oxo-2'-deoxyguanosine in lymphocyte DNA does not correlate with the concentration of antioxidant vitamins in blood plasma.

2001 ◽  
Vol 48 (2) ◽  
pp. 535-539 ◽  
Author(s):  
D Gackowski ◽  
M Ciecierski ◽  
A Jawień ◽  
R Oliński
Keyword(s):  
Ascorbic Acid ◽  
Background Level ◽  
Antioxidant Vitamins ◽  
Alpha Tocopherol ◽  
Free Radical Scavengers ◽  
Radical Scavengers ◽  
Endogenous Level ◽  
The Mean ◽  
Cellular Dna ◽  
The Relationship

Antioxidant vitamins, being effective free radical scavengers, can protect cellular DNA from oxidative damage. Therefore, in the present study we report on the relationship between basal level of 8-oxo-2'-deoxyguanosine in human lymphocyte DNA and the concentration of antioxidant vitamins (A, C and E). The average level of 8-oxo-2'-deoxyguanosine in lymphocytes of the studied group (15 males and 20 females) was 9.57 per 10(6) dG molecules. The endogenous level of ascorbic acid (vitamin C) in the plasma was, on average, 56.78 microM, while the mean concentrations of retinol (vitamin A) and alpha-tocopherol (vitamin E) were 1.24 uM and 25.74,uM, respectively. No correlations were found between individual 8-oxo-2 micro-deoxyguanosine levels in lymphocyte DNA and endogenous concentration of the vitamins.

Changes in lipid peroxidation during pregnancy and after delivery in rats: effect of pinealectomy

Reproduction ◽  
2000 ◽  
pp. 143-149 ◽  
Author(s):  
RM Sainz ◽  
RJ Reiter ◽  
JC Mayo ◽  
J Cabrera ◽  
DX Tan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Oxidative Damage ◽  
Energy Demand ◽  
Physiological State ◽  
High Energy ◽  
Free Radical Scavengers ◽  
Radical Scavengers ◽  
Oxygen Requirement ◽  
Pregnant Rats

Pregnancy is a physiological state accompanied by a high energy demand of many bodily functions and an increased oxygen requirement. Because of the increased intake and utilization of oxygen, increased levels of oxidative stress would be expected. In the present study, the degree of lipid peroxidation was examined in different tissues from non-pregnant and pregnant rats after the delivery of their young. Melatonin and other indole metabolites are known to be direct free radical scavengers and indirect antioxidants. Thus the effect of pinealectomy at 1 month before pregnancy on the accumulation of lipid damage was investigated in non-pregnant and pregnant rats after the delivery of their young. Malonaldehyde and 4-hydroxyalkenal concentrations were measured in the lung, uterus, liver, brain, kidney, thymus and spleen from intact and pinealectomized pregnant rats soon after birth of their young and at 14 and 21 days after delivery. The same parameters were also evaluated in intact and pinealectomized non-pregnant rats. Shortly after delivery, lipid oxidative damage was increased in lung, uterus, brain, kidney and thymus of the mothers. No differences were detected in liver and spleen. Pinealectomy enhanced this effect in the uterus and lung. It is concluded that during pregnancy high levels of oxidative stress induce an increase in oxidative damage to lipids, which in some cases is inhibited by the antioxidative actions of pineal indoles.

Nutritional aspects and their influences on the pathophysiology of

2014 ◽  
Vol 23 (1) ◽  
pp. 33
Author(s):  
Nathalia Liberato Nascimento ◽  
Iwyson Henrique Fernandes da Costa ◽  
Rivelilson Mendes de Freitas
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fatty Acids ◽  
Folic Acid ◽  
Saturated Fatty Acids ◽  
Free Radical Scavengers ◽  
Radical Scavengers ◽  
High Intake ◽  
Neuroprotective Effects ◽  
Nutritional Factors

The objective of this study was to conduct a review about the nutritional aspects and their influences on the pathophysiology of Alzheimer’s disease. The review describes the pathophysiology of Alzheimer’s disease, the generally indicated diets, and the nutritional factors that may aggravate the disease based on a literature review using the following keywords in English and Portuguese: “Alzheimer’s disease”, “physiopathology”, “nutritional aspects”, and “antioxidants”. A total of 100 articles were found, 48 in Lilacs and 52 in MedLine, but only 54 articles were selected for the review. The use of antioxidants as free radical scavengers is generally indicated in diets for Alzheimer’s patients. Studies also suggest that caffeine, vitamin B12, and folic acid have neuroprotective effects. Cohort studies found that a high intake of saturated fatty acids and obesity increase the risk of Alzheimer’s disease. People with Alzheimer’s disease should avoid diets high in carbohydrates and saturated fats, and prefer foods high in antioxidants.Keywords: Alzheimer disease; Antioxidants; Neurophysiology; Review literture as topic.

scholarly journals Oxidative hemolysis of erythrocytes and its inhibition by free radical scavengers.

1988 ◽  
Vol 263 (36) ◽  
pp. 19809-19814
Author(s):  
E Niki ◽  
E Komuro ◽  
M Takahashi ◽  
S Urano ◽  
E Ito ◽  
...  
Keyword(s):  
Free Radical ◽  
Free Radical Scavengers ◽  
Radical Scavengers ◽  
Oxidative Hemolysis

Novel C-9, 9'-O-acyl Esters of (-)-Carinol as Free-radical Scavengers and Xanthine Oxidase Enzyme Inhibitors: Synthesis and Biological Evaluation

2013 ◽  
Vol 9 (1) ◽  
pp. 100-103 ◽  
Author(s):  
Praveen Kumar Suryadevara ◽  
Hari Babu Tatipaka ◽  
Rama Subba Rao Vidadala ◽  
Ashok k Tiwari ◽  
Janaswamy Madhusudana Rao ◽  
...  
Keyword(s):  
Free Radical ◽  
Xanthine Oxidase ◽  
Enzyme Inhibitors ◽  
Biological Evaluation ◽  
Free Radical Scavengers ◽  
Radical Scavengers ◽  
Oxidase Enzyme ◽  
Synthesis And Biological Evaluation
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