Nitric oxide covalently labels a 6-hydroxydopa-derived free radical intermediate in the catalytic cycle of copper/quinone-containing amine oxidase from lentil seedlings

2005 ◽  
Vol 386 (1) ◽  
Author(s):  
Silvia Longu ◽  
Alessandra Padiglia ◽  
Jens Z. Pedersen ◽  
Alessandro Finazzi Agrò ◽  
Anna Mura ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Free Radical ◽  
Amine Oxidase ◽  
Catalytic Cycle ◽  
Radical Intermediate ◽  
Free Radical Intermediate

A substrate-cofactor free radical intermediate in the reaction mechanism of copper amine oxidase

Biochemistry ◽  
1992 ◽  
Vol 31 (1) ◽  
pp. 8-12 ◽  
Author(s):  
Jens Z. Pedersen ◽  
Said El-Sherbini ◽  
Alessandro Finazzi-Agro ◽  
Giuseppe Rotilio
Keyword(s):  
Free Radical ◽  
Reaction Mechanism ◽  
Amine Oxidase ◽  
Radical Intermediate ◽  
Copper Amine Oxidase ◽  
Free Radical Intermediate ◽  
Copper Amine

Photochemical decomposition of t-butyl hydroperoxide; Photocatalytical effects of VO(II) and Co(III) 2,4-pentanedionates

1988 ◽  
Vol 53 (3) ◽  
pp. 497-505 ◽  
Author(s):  
Stanislav Luňák ◽  
Aleksandr I. Kokorin ◽  
Eva Mácová ◽  
Pavel Lederer
Keyword(s):  
Free Radical ◽  
Opposite Effect ◽  
Radical Intermediate ◽  
Butyl Hydroperoxide ◽  
Free Radical Intermediate ◽  
Catalytically Active ◽  
Photochemical Decomposition ◽  
Epr Signal

It has been found that [VO(acac)2] and [Co(acac)3] increase the rate of t-BuOOH photolysis, whereas [Fe(acac)3] has the opposite effect. Redox changes of the catalytically active [VO(acac)2] were followed using the EPR technique. An EPR signal from a free radical intermediate of photochemical decomposition of t-BuOOH was recorded, and the concentration of the intermediate was monitored during the reaction.

scholarly journals A stable free radical intermediate in the reaction of 2-oxoacid:ferredoxin oxidoreductases of Halobacterium halobium

FEBS Letters ◽  
1980 ◽  
Vol 118 (2) ◽  
pp. 271-273 ◽  
Author(s):  
R. Cammack ◽  
L. Kerscher ◽  
D. Oesterhelt
Keyword(s):  
Free Radical ◽  
Halobacterium Halobium ◽  
Radical Intermediate ◽  
Stable Free Radical ◽  
Free Radical Intermediate

scholarly journals Free radical intermediate in the N-demethylation of aminopyrine by catalase-cumene hydroperoxide system.

1980 ◽  
Vol 28 (2) ◽  
pp. 683-685 ◽  
Author(s):  
HIROTERU SAYO ◽  
MIKIO HOSOKAWA
Keyword(s):  
Free Radical ◽  
Cumene Hydroperoxide ◽  
Radical Intermediate ◽  
Free Radical Intermediate

Spin trapping of a free radical intermediate formed during microsomal metabolism of hydrazine

1985 ◽  
Vol 133 (3) ◽  
pp. 1086-1091 ◽  
Author(s):  
Atsuko Noda ◽  
Hiroshi Noda ◽  
Kohji Ohno ◽  
Toshiaki Sendo ◽  
Ayako Misaka ◽  
...  
Keyword(s):  
Free Radical ◽  
Spin Trapping ◽  
Radical Intermediate ◽  
Microsomal Metabolism ◽  
Free Radical Intermediate

Activity of the Novel Ribonucleotide Reductase Inhibitor Didox on Human and Murine Models of Acute Leukemia,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3637-3637
Author(s):  
Guerry J Cook ◽  
Howard L Elford ◽  
Timothy Pardee
Keyword(s):  
Free Radical ◽  
Cell Lines ◽  
Mechanism Of Action ◽  
Ribonucleotide Reductase ◽  
Survival Benefit ◽  
Reductase Inhibitor ◽  
Radical Intermediate ◽  
Pilot Studies ◽  
Ribonucleotide Reductase Inhibitor ◽  
Free Radical Intermediate

Abstract Abstract 3637 Acute Myeloid Leukemia (AML) is an aggressive, genetically heterogeneous disease wherein immature myeloid progenitors crowd out the normal hematopoietic cells leading to marrow failure and ultimately death. Each year in the United States there are approximately 12,000 new cases and 9,000 deaths from AML. Combination chemotherapy of an anthracycline and cytarabine has remained the mainstay of frontline treatment despite decades of active research. Treatment will often lead to a remission; however, the majority of patients relapse with chemoresistant disease. This highlights the need for the development of new therapies for patients. The Ribonucleotide Reductase (RR) reaction facilitates the conversion of ribonucleotides to deoxyribonucleotides via a free radical intermediate and is the rate-limiting step in DNA replication. The anti-tumor activity of Hydroxyurea is due to its ability to quench the free radical intermediate generated at the M2 subunit of RR ultimately resulting in a depletion of the cell's deoxyribonucleotide pool. This chemotherapeutic is useful for the palliative treatment of AML; however, its myelosuppressive effects are dose limiting. 3,4-Dihydroxybenzohydroamic acid (Didox) is a RR inhibitor with a mechanism of action similar to that of Hydroxyurea that has been shown to be less myelosuppressive in an animal model. Didox has been examined for toxicity in Phase I and Phase II trials in the United Kingdom in several malignancies. These clinical trials have reported Didox to be well tolerated at 6 g/m2. Major dose limiting organ toxicities were hepatic and renal. Given this low toxicity and mechanism of action we tested the activity of Didox in pilot studies of human and murine leukemias. In vitro studies were done to assess the Inhibitory Concentration (IC50) against five human AML cell lines, KG1a, OCI-AML3, THP-1, HL60 and K562. Cells were exposed to a titration of Didox for 72 hours and viability determined. The average IC50 of Didox was 5.76 μM (Range 3.62–7.37 μM). Initial In vivo studies were carried out in a syngeniec, therapy resistant MLL-ENL driven AML model. Murine leukemias were injected into sublethally irradiated recipients and allowed to engraft. Animals were given five days of Didox 425 mg/kg or a control treatment via intraperitoneal injection. Response and survival data were collected. A nimals tolerated the therapy well. Treated animals demonstrated a significant survival benefit in two separately derived MLL leukemias (one expressing the Flt3-ITD and one expressing NRasG12D) with p values of 0.0094 and 0.009 respectively. To determine the efficacy of Didox against a murine Acute Lymphoblastic Leukemia (ALL) model we injected syngeniec Balb/c mice with Baf3 cells engineered to express the p210 BCR-ABL fusion protein. We found that while the animals tolerated Didox, treatment did not provide a survival benefit, p =0.3581. This suggests that the use of Didox would be more efficacious in the treatment of AML than in ALL. Didox is a novel ribonucleotide reductase inhibitor with IC50 values in the low micromolar range for a panel of human and murine cell lines. Pilot studies in our syngeneic mouse models show that Didox is well tolerated in AML and ALL. Moreover, Didox demonstrates a survival benefit in chemoresistant murine AMLs. This data would imply Didox has activity in AML and additional studies to further characterize its activity are underway. Disclosures: Elford: Molecules for Health: Equity Ownership, Patents & Royalties.

Sign in / Sign up

Export Citation Format

Share Document