Electron transfer mechanism for regulatory action by nitric oxide

Kovacic, Peter

doi:10.1016/0302-4598(95)01888-3

Cited by 17 publications

(10 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other modes of action may be involved, e.g., indirectly by interaction with metal to form complexes capable of redox cycling [106]. Also, this simple molecule is known to undergo metabolism to nitric oxide (NO) [174], which can generate OS [175]. Hydroxyurea has also been used for treatment of HIV infections and sickle cell anemia [173].…”

Section: Hydroxyureamentioning

confidence: 99%

Mechanisms of Anti-Cancer Agents Emphasis on Oxidative Stress and Electron Transfer

Kovacic

Osuna²

2000

CPD

Self Cite

150

105

View full text Add to dashboard Cite

A large body of evidence has accumulated indicating involvement of oxidative stress (OS) in the mode of action of various bioactive substances, including those of the immune system. The data for anticancer drugs (main and miscellaneous) are summarized herein. Although diverse origins pertain, reactive oxygen species (ROS) are frequently generated by redox cycling via electron transfer (ET) groups, such as quinones (or phenolic precursors), metal complexes (or complexors), aromatic nitro compounds (or reduced products) and conjugated imines (or iminium species). We believe it is not coincidental that these functionalities are frequently found in anticancer agents or their metabolites. Generally, the ET moieties display reduction potentials in the physiologically active range. Often ROS are also implicated in more traditional rationales, namely, enzyme inhibition, membrane or DNA insult, and interference with DNA or protein synthesis. A multi-faceted approach to mechanism appears to be the most logical. Significantly, the unifying theme of ET-OS also applies to other drug categories, as well as to toxins, carcinogens, hormones, and enzymes. Since this theoretical framework aids in our understanding of drug action, it can serve as a useful tool in the design of more active and safer pharmaceuticals.

show abstract

Section: Hydroxyureamentioning

confidence: 99%

Mechanisms of Anti-Cancer Agents Emphasis on Oxidative Stress and Electron Transfer

Kovacic

Osuna²

2000

CPD

Self Cite

150

105

View full text Add to dashboard Cite

show abstract

“…Other reports address NO in CV toxicity [80,81]. Several reviews present the case for ET-ROS-OS in the biochemistry of NO [11,82].…”

Section: Nitric Oxidementioning

confidence: 96%

Cardiovascular Toxicity from the Perspective of Oxidative Stress, Electron Transfer, and Prevention by Antioxidants

Kovacic¹,

Thurn²

2005

CVP

Self Cite

View full text Add to dashboard Cite

show abstract

“…In relation to basic molecular events (7,(38)(39)(40), an initiating step may be complexation with iron. A number of ways can be imagined whereby ET could occur after fixation.…”

Section: Nitric Oxide Inductionmentioning

confidence: 99%

“…Abundant reports exist dealing with cell signaling and associated redox processes and ROS, particularly in relation to neurotransmission by NO (7,(38)(39)(40). NO is a major player in controlling cell and organ operations, and it has been designated the most widespread signaling molecule.…”

Section: Nitric Oxide Inductionmentioning

confidence: 99%

See 1 more Smart Citation

Fundamental, Electron Transfer Mechanism by Pyrylium-Type Ions for the Anticancer Drugs 5,6-Dimethylxanthenone-4-Acetic Acid (DMXAA) and Flavone-8-Acetic Acid (FAA)

Kovacic

2005

CMCACA

View full text Add to dashboard Cite

Pyrylium-type salts derived from DMXAA and FAA are proposed to play an important mechanistic role in anticancer action. Electron transfer (ET) processes apparently initiate cell signaling cascades that lead to the observed effects, such as, antivascular influences, cytokine induction, and apoptosis. Possible participation of nitric oxide and serotonin is discussed. Structure-activity relationships involving DMXAA, FAA, acridines, and quinolines support the hypothetical framework, as well as electrochemistry and photochemistry. Similarity is pointed out to the action of plant hormones, e.g. ethylene. Involvement of ET pathways places the cationic salts within the general mechanistic framework for other anticancer agents. Other drug activities of xanthenones are in accord with the ET approach. Insight into fundamental mechanistic aspects should aid in development of improved drugs in this class through rational design.

show abstract

Electron transfer mechanism for regulatory action by nitric oxide

Cited by 17 publications

References 50 publications

Mechanisms of Anti-Cancer Agents Emphasis on Oxidative Stress and Electron Transfer

Mechanisms of Anti-Cancer Agents Emphasis on Oxidative Stress and Electron Transfer

Cardiovascular Toxicity from the Perspective of Oxidative Stress, Electron Transfer, and Prevention by Antioxidants

Fundamental, Electron Transfer Mechanism by Pyrylium-Type Ions for the Anticancer Drugs 5,6-Dimethylxanthenone-4-Acetic Acid (DMXAA) and Flavone-8-Acetic Acid (FAA)

Contact Info

Product

Resources

About