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Biomedical subjects

M D Ryan

Publications and source records attributed to M D Ryan.

At least 73 records · Page 4Linked to original sources
PubMed1988

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 antitumor agents, bipyridine, phenanthroline, hydroxyurea, diethyldithiocarbamate, and alpha, alpha'-bis(8-hydroxyquinolin-7-yl)-4-methoxytoluene. The favorable reduction potentials ranged from +0.5 to -0.5 Electrochemical behavior is correlated in some cases with structure and physiological activity. Relevant literature data are discussed.

Antineoplastic Agents↗
PubMed1987

Mode of action of antiprotozoan agents. Electron transfer and oxy radicals.

Cyclic voltammetry data were obtained for most of the main classes of antiprotozoan agents, specifically, nitroheterocycles, quinones, metal complexes and derivatives, iminium-type ions, and azo compounds. The reductions were generally reversible in the range of -0.3 to -0.9 V. Catalytic production of oxidative pressure from redox cycling involving oxygen is believed to be an important mode of action by the medicinal agents. Literature data contribute support.

Antiprotozoal Agents↗
PubMed1987

Cyclic voltammetry of quinolinium salts and related compounds: correlation with structure and anticancer activity.

Cyclic voltammetry data were obtained for 12 salts of quinolines, one pyridine, and one open-chain imine which possess varying degrees of anticancer activity. The structural features include sidechain bis(2-methylthio)vinyl, 2-methylthio-2-aminovinyl, dithioacetic acid, 2-quinolylvinyl, 2-styrylvinyl, and guanidine sulfide functionalities. Reduction potentials ranged from -0.43 to -1.08 V. The electrochemical results are correlated with structure. A possible mechanism of anticancer action is addressed.

Antineoplastic Agents↗
PubMed1987

An integrated concept of amebicidal action: electron transfer and oxy radicals.

Cyclic voltammetry data were obtained for most of the main categories of antiamebic agents, specifically, quinones, heterocyclic nitro compounds, metal derivatives and chelators, and iminium-type ions. The reductions (our data and literature values) were for the most part reversible, with potentials usually in the favorable range of +0.10 to -0.56 V. The drug effect is believed to result generally from the catalytic production of oxidative stress usually arising from the formation of superoxide via electron transfer. In addition, relevant literature data are provided.

Amebicides↗
PubMed1987

Charge transfer-oxy radical mechanism for anticancer agents: mAMSA derivatives, rhodamine 123, and nickel salicylaldoximate.

The proposal is advanced that many anticancer agents may function via redox reactions resulting in generation of toxic oxy radicals which destroy neoplastic cells. Cyclic voltammetry was performed with some of the main types: iminium ions (protonated mAMSA derivatives), quinone derivatives (rhodamine 123) and metal complexes (nickel(II) salicylaldoximate). In addition, relevant literature data are provided. A rationale is offered that relates electrochemical data to physiological activity.

Amsacrine↗
PubMed1987

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.

Amsacrine↗
PubMed1986

Cyclic voltammetry of phenazines and quinoxalines including mono- and di-N-oxides. Relation to structure and antimicrobial activity.

Cyclic voltammetry data were obtained for eight phenazines and phenazine-N-oxides, and eleven quinoxalines and quinoxaline-N-oxides: 1,6-phenazine-diol-5,10-dioxide (iodinin), iodinin copper complex, 6-methoxy-1-phenazinol-5,10-dioxide 1,6-dimethoxyphenazine-5-oxide, 1,6-phenazinediol, 1,6-dimethoxyphenazine, quinoxaline-1,4-dioxide, 2-methylquinoxaline-1,4-dioxide, 2,3-diphenylquinoxaline-1,4-dioxide, 2-carboxyquinoxaline-1,4-dioxide, 5-hydroxyquinoxaline-1,4-dioxide, 5-hydroxy-8-methoxyquinoxaline-1,4-dioxide, 2-methylquinoxaline, 2,3-diphenylquinoxaline, 5-hydroxyquinoxaline, 5-hydroxy-8-methoxyquinoxaline and 2-(2-quinoxalinylmethylene)hydrazine carboxylic acid methyl ester-1,4-dioxide (Carbadox). The di-N-oxides exhibit the most positive E1/2 values within each class. Reversible first wave reductions were observed for iodinin, iodinin copper complex, 1,6-dimethoxyphenazine-5-oxide, 1,6-dimethoxyphenazine, quinoxaline-1,4-dioxide, 2-methylquinoxaline-1,4-oxide and 2,3-diphenylquinoxaline-1,4-dioxide. The results are correlated with structure. Some relationships exist between reduction potential and reported antimicrobial activity. A possible mechanism of drug action is addressed.

Anti-Bacterial Agents↗
PubMed1986

Conjugated and cross-conjugated mesomeric betaines. Correlation of electroreduction with structure and physiological activity.

Electroreduction studies were performed on several cross-conjugated mesomeric betaines containing the fused pyrazolium (2) and fused imidazolium (3) ring systems. Studies at acidic pH were of principal interest. Substituent effects for 2 were in line with prior findings, and reduction potentials were comparatively negative (-0.96 to -1.34 V). Reduction potentials fit the modified Hammett equation. Compound 3 was more readily reduced (-0.88 V). The related psi-oxatriazoles (6) gave values in the range of -0.85 to -1.22 V. The electrochemical characteristics are compared with those of the mesoionic sydnones (4) and sydnoneimines (5). These mesoionic compounds were generally reduced at more positive potentials than 2 and 3. A relationship between electroreduction and physiological activity is proposed. The overall results are in keeping with the hypothesis of widespread participation of iminium-type species in biological systems.

Electrochemistry↗
PubMed1986

Mechanism of antibacterial action: electron transfer and oxy radicals.

Most of the main categories of bactericidal agents, namely, aliphatic and heterocyclic nitro compounds, metal derivatives and chelators, quinones, azo dyes, and iminium-type ions, are proposed to exert their action by a unified mechanism. The toxic effect is believed to result generally from the catalytic production of reactive oxygen radicals that usually arise via electron transfer. Cyclic voltammetry was performed on a number of these agents. Reductions were for the most part reversible, with potentials in the favorable range of -0.20 to -0.58 V.

Alkylating Agents↗
PubMed1986

Oxidative ionic metabolites of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): correlation of electroreduction with physiological behavior.

Electrochemical studies (reduction potential and reversibility) were performed on 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-2,3-dihydropyridinium (MPDP+). MPP+ gave reduction potentials in the range of -1.09 to -1.11 V in organic solvents in a process which was reversible. The reduction potential of MPDP+ was -0.64 V (irreversible). Possible relationships involving the electrochemical properties, oxy radical formation, and biological activity of these and related iminium species are discussed.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

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.

Alkylation↗
PubMed1986

Bolt-plate fixation for anterior spinal fusion.

A bolt-plate device for fixation of distal thoracic and proximal lumbar vertebral bodies has proved effective in a variety of surgical situations. The instrumentation is designed to obtain the optimum conditions for the healing of cancellous bone, namely, rigid immobilization and, if possible, close apposition of surfaces. The device may also be effectively employed to protect grafts used to replace a vertebral body.

Bone Plates↗
PubMed1985

Bilateral fatigue fractures of the distal fibulae caused by a change of running shoes.

A 26-year-old man sustained bilateral, symmetrical fatigue fractures of his distal fibulae while running in a 14-km road race. He had trained repeatedly over the course without developing any symptoms, but on the day of the race he lost one of his regular running shoes. He competed instead in old, borrowed tennis shoes. After running over a distance of 2 km, he felt pain about 4 cm above the distal end of both fibulae. Two weeks later, radiographs showed bilateral fractures. The change of footwear was the only identifiable factor in the causation of these fractures. Analysis by compression-loading showed that his usual running shoes absorbed twice as much energy and deformed five times as much as those used in the race.

Adult↗
PubMed1985

Charge transfer in the mechanism of drug action involving quinoxaline di-N-oxides.

Cyclic voltammetry data were obtained for various 2,3-disubstituted quinoxaline di-N-oxides: dimethyl, bishydroxymethyl, bisacetoxymethyl, bis-N-anilinomethyl, and dicarboxaldehyde hydrate. The dimethyl derivative exhibited the most negative E1/2 value, and along with the diol, showed reversible reduction for the first wave. Rationalizations of the E1/2 values are provided. Reasonable correlations exist for the electrochemical data and drug activity. The results support the diiminium theory of drug action.

Anti-Bacterial Agents↗
PubMed1985

Charge transfer and oxy radicals in antimalarial action. Quinones, dapsone metabolites, metal complexes, iminium ions, and peroxides.

A mechanism of action is proposed that encompasses almost all of the main categories of antimalarial agents: quinones and precursors, dapsone metabolites, metal complexes of thiosemicarbazones and biguanides, iminium-type ions from acridines and quinolines, and peroxides. The toxic effect of the drugs is believed to result from the generation of reactive oxygen radicals that usually arise via charge transfer. Electrochemical studies (reduction potential and reversibility) were performed on a number of these agents. Reduction potentials range from -0.23 to -1.52 V. It is likely that the in vivo values are appreciably more positive in certain cases.

Aminacrine↗