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N O'Sullivan

Publications and source records attributed to N O'Sullivan.

11 recordsLinked to original sources
PubMed1994

Cyclopropamitosenes, novel bioreductive anticancer agents. Synthesis, electrochemistry, and biological activity of 7-substituted cyclopropamitosenes and related indolequinones.

The synthesis of the indolequinones 8 and 9 starting from methyl 4-(benzyloxy)-5-methoxy-indole-2-carboxylate (10) is described. The methoxy group in the indolequinones 1, 2, 4, 5, and 7-9 can be displaced by various nitrogen nucleophiles (ammonia, 2-methoxyethylamine, aziridine, 2-methylaziridine, pyrrolidine) in 22-88% yield. The resulting amino-substituted quinones, together with their methoxy precursors, were studied by cyclic voltammetry to determine their reduction potentials, which, in DMF solution, lie in the range -1.355 to -1.597 V (vs ferrocene). The cytotoxicity of the compounds towards aerobic and hypoxic mammalian cells was also determined; in general, under aerobic conditions, the cyclopropamitosenes are more toxic than the corresponding pyrrolo[1,2-a]indolequinones, which are in turn more toxic than the simple 1,2-dimethylindolequinones, with many of the compounds in each series showing greater toxicity toward hypoxic cells.

Animals↗
PubMed1994

Cyclopropamitosenes: novel bioreductive anticancer agents--mechanism of action and enzymic reduction.

The mechanism of action of cyclopropamitosenes, novel bioreductive anticancer agents, has been investigated using a unique combination of chemical and biochemical techniques. The compounds 4 function as reductively activated alkylating agents under chemical reducing conditions, and the biochemical experiments establish that the methoxy- and aziridinyl-derivatives 4a and 4b behave differently upon bioreduction.

Alkylating Agents↗
PubMed1992

Pharmacokinetics and tissue penetration of ampicillin and brobactam following oral administration of 2085P.

Eight healthy volunteers received a 1,000-mg single oral dose of 2085P which consisted of 800 mg of pivampicillin and 200 mg of brobactam. Concentrations of ampicillin and brobactam in plasma, inflammatory fluid, and urine were measured over the subsequent 24 h. Pivampicillin and brobactam were moderately rapidly absorbed. The mean (standard deviation) maximum concentration in plasma (Cmax) of ampicillin was 8.2 (1.9) micrograms/ml, and that of brobactam was 2.1 (2.0) micrograms/ml at mean times of 1.9 (0.5) and 2.3 (0.8) h, respectively. The elimination half-lives in plasma were 1.8 (0.5) and 1.6 (2.0) h, respectively. Both agents penetrated the experimentally induced inflammatory fluid, reaching a mean maximum at 3 h. The Cmax of ampicillin was 6.8 (2.3) micrograms/ml, and that of brobactam was 1.0 (0.4) micrograms/ml. The penetration (derived by comparing the area under the concentration-time curve from 0 h to infinity for inflammatory fluid with that for plasma) was 97.3% (26.0%) for ampicillin and 81% (22.3%) for brobactam. The 24-h urinary recovery was 54.2% (16.6%) of the administered dose for ampicillin and 40.2% (11.4%) for brobactam. These data suggest that this combination of beta-lactam and inhibitor should be efficacious in treating infections caused by ampicillin-resistant pathogens.

Administration, Oral↗
PubMed1991

Pharmacokinetics and tissue penetration of rufloxacin, a long acting quinolone antimicrobial agent.

The pharmacokinetics of rufloxacin after a single 400 mg oral dose were studied in eight volunteers, measuring plasma, inflammatory fluid and urine concentrations. Mean peak plasma concentrations of 4.4 mg/L were achieved at a mean time of 1.9 h after administration. The mean plasma elimination half-life was 28.2 h. Mean peak levels in inflammatory fluid reached 3.2 mg/L after 3.5 h, and 30.7% of the dose was eliminated in urine by 96 h. The apparent mean volume of distribution of rufloxacin, at steady state, was 109.5 L. The mean percentage penetration of rufloxacin into the inflammatory exudate, as measured by ratios of AUC0-50 h was 90%.

Administration, Oral↗
PubMed1990

Lectin typing of Campylobacter isolates.

Isolates of Campylobacter jejuni, C coli, C fetus and C laridis were tested for agglutination reactions with a panel of five lectins: Arachis hypogaea, Bauhinia purpurea, Solanum tuberosum, Triticum vulgaris and Wisteria floribunda. Twenty three patterns of agglutination (lectin types) were recorded among 376 isolates. Patterns were consistent and reproducible. Only 4.5% of isolates were untypable because of autoagglutination. Some lectin types were found exclusively or predominantly in a species, but others were shared between species. Forty two per cent of C jejuni and 35% of C coli isolates belonged to lectin type 4. There was no apparent correlation between lectin type and serotype; different lectin types were found among strains of single Penner and Lior serotypes. Lectin typing is a simple and economical procedure suitable for use in non-specialist laboratories, either as an adjunct to serogrouping or, after further development, as a sole typing scheme.

Agglutination Tests↗
PubMedDate not supplied

Harlequin colour in the Great Dane dog.

Breeding data from Eire and Great Britain confirm the hypothesis of Sponenberg (1985) that the harlequin colour of the Great Dane breed of dog is due the combined action of a dominant gene H with the merle gene M in the genotype H+M+. The typical bluish coloration induced by M is modified to white by the action of H. The H gene is a prenatal lethal when homozygous HH and this study offers clear indication that the heterozygous H+ interacts with M to reduce the viability of white merle homozygotes H+MM.

Animals↗