An Integrated Concept of Carcinogenic-Anticarcinogenic Action

Author Institution: Department of Chemistry and Chemical Engineering, Case Institute of Technology, Cleveland, Ohi

Electron Transfer-oxy Radical Mechanism for Anti-cancer Agents: 9-anilinoacridines

A possible mode of action involving electron transfer is advanced for the 9- anilinoacridines. The mechanism entails formation of toxic oxy radicals which destroy the neoplasm. Cyclic voltammetry was performed on iminium type ions derived by protonation of the acridines. Reductions were generally reversible with potentials of about - 0.60 V. Involvement of quinoidal metabolites is also a possibility. The relationship of electrochemical behavior to structure and physiological activity is addressed

Zolpidem, a clinical hypnotic that affects electronic transfer, alters synaptic activity through potential GABA receptors in the nervous system without significant free radical generation

Zolpidem (trade name Ambien) has attracted much interest as a sleep-inducing agent and also in research. Attention has been centered mainly on receptor binding and electrochemistry in the central nervous system which are briefly addressed herein. A novel integrated approach to mode of action is presented. The pathways to be discussed involve basicity, reduction potential, electrostatics, cell signaling, GABA receptor binding, electron transfer (ET), pharmacodynamics, structure activity relationships (SAR) and side effects. The highly conjugated pyridinium salt formed by protonation of the amidine moiety is proposed to be the active form acting as an ET agent. Extrapolation of reduction potentials for related compounds supports the premise that zolpidem may act as an ET species in vivo. From recent literature reports, electrostatics is believed to play a significant role in drug action

Clinical physiology and mechanism of dizocilpine (MK-801): Electron transfer, radicals, redox metabolites and bioactivity

Dizocilpine (MK-801), an extensively investigated drug possessing secondary amine and benzenoid functions, displays a wide array of biological properties, including anticonvulsant and anesthetic. There is scant discussion of biomechanism. A relevant, important finding is formation of oxidative metabolites in the hydroxylamine and phenolic categories. Analogy to cocaine metabolites suggests participation of redox entities, such as, hydroxylamine, nitroxide and nitrosonium, which can lead to electron transfer and radical formation. There is also similarity to metabolism by 3,3′-iminodipropionitrile and phencyclidine. Alternatively, the phenolic metabolites are well-known precursors of ET quinones. The review documents various physiological effects, mainly involving the central nervous system. Also of interest are the pro- and anti-oxidant properties. Considerable attention has been paid to MK-801 as an antagonist of the N-methyl-D-aspartate receptor in the glutamate category. This aspect is often associated with effects on the central nervous system. The review also provides recent literature dealing with MK-801/NMDA receptor in various areas of bioactivity. Studies were made of MK-801 involvement in working memory processing. Deficits in behavior were noted after administration of the drug. Treatment of mice with dizocilpine induced learning impairment. The influence of MK-801 on fear has been investigated. The substance is known to exert an analgesic effect in pain control. A number of reports deal with anesthetic properties

Novel, unifying mechanism for mescaline in the central nervous system: Electrochemistry, catechol redox metabolite, receptor, cell signaling and structure activity relationships

A unifying mechanism for abused drugs has been proposed previously from the standpoint of electron transfer. Mescaline can be accommodated within the theoretical framework based on redox cycling by the catechol metabolite with its quinone counterpart. Electron transfer may play a role in electrical effects involving the nervous system in the brain. This approach is in accord with structure activity relationships involving mescaline, abused drugs, catecholamines and etoposide. Inefficient demethylation is in keeping with the various drug properties, such as requirement for high dosage and slow acting

Anti-cancer Action of Metal Complexes: Electron Transfer and Oxidative Stress?

Evidence is presented in support of an electron transfer mechanism for various metal complexes possessing anti-neoplastic properties. Cyclic voltammetry was performed on several metallocenes, bis(acetato)bis(imidazole)Cu(II), and coordination compounds (Cu or Fe) of the anti-tumor agents, bipyridine, phenanthroline, hydroxyurea, diethyldithiocarbamate, and α, α1-bis(8-hydroxyquinolin-7-yl)-4-methoxytoluene. The favorable reduction potentials ranged from +0.5 to -0.5 V. Electrochemical behavior is correlated in some cases with structure and physiological activity. Relevant literature data are discussed

SOA Adoption Phases - A Case Study

The paper argues that attitudes to SOA follow a typical hype cycle from Technological Trigger, Peak of Inflated Expectations, and a Trough of Disillusionment to the more recent realization that SOA is a concept that may offer certain benefits but has several limitations. Themain research question studies how the attitude to SOA changes in various phases of the hype cycle, how the SOA implementation cycle and an increase in business process maturity (BPMa) are interconnected and which factors influence the transition between the hype cycle phases. The paper shows that an organization’s success with implementing SOA depends on its ability to match the SOA implementation with an increase in BPMa. The dual purpose of implementing SOA is shown in the first framework: to assure the coherence of IT assets and to assure business/IT alignment. In the second framework, the interconnection of SOA and BPMa and its role in transiting through the hype cycle phases is outlined. The findings are analyzed using a longitudinal case study of a large Slovenian company

Charge Transfer-oxy Radical Mechanism for Anti-cancer Agents

The proposal is advanced that anti-cancer drugs generally function by charge transfer resulting in formation of toxic oxy radicals which destroy the neoplasm. Electrochemical studies were performed with some of the main types of agents: iminium ions (adenine iminium from alkylating species, iminium metabolite of 6-mercaptopurine, nitidine, other polynuclear iminiums) and metal complexes (Pt(II)diaquodiammine-guanosine, copper salicylaldoximes). Reduction potentials ranged from -0.4 to -1.2 V. Literature data for quinones are presented and radiation is discussed. Based on the theoretical framework, a rationale is offered for the carcinogen-anti-cancer paradox and the role of antioxidants

Random polarization dynamics in a resonant optical medium

Random optical-pulse polarization switching along an active optical medium in the $\Lambda$-configuration with spatially disordered occupation numbers of its lower energy sub-level pair is described using the idealized integrable Maxwell-Bloch model. Analytical results describing the light polarization-switching statistics for the single self-induced transparency pulse are compared with statistics obtained from direct Monte-Carlo numerical simulations.Comment: 7 pages, 3 figure