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Guy Carter

Publications and source records attributed to Guy Carter.

4 recordsLinked to original sources

Pharmaceutical profiling method for lipophilicity and integrity using liquid chromatography-mass spectrometry.

A method is described for the simultaneous profiling of sample lipophilicity, integrity, and purity. The method is rapid and is applicable to high throughput profiling of pharmaceutical properties in drug discovery. A short Polaris C(18) column is used with a rapid, wide-polarity mobile phase gradient, UV detection, and MS analysis. The lipophilicity of each component is estimated from a calibration curve using six drug or organic compounds and plotting their respective measured retention time versus LogD(7.4) (literature). The correlation of LogD(7.4) (literature) to LogD(7.4) (HPLC) for 60 structurally diverse drugs has a correlation coefficient r(2) of 0.89. The method is applicable to compounds with MW>200 and retention time>1.5 min for rapid, initial pharmaceutical profiling in drug discovery.

Chromatography, High Pressure Liquid↗

Novel alpha-pyrones produced by a marine Pseudomonas sp. F92S91: taxonomy and biological activities.

Inhibitors of the enzymes involved in fatty acid biosynthesis (FAB) have been reported as antibacterial agents. These include thiolactomycin, cerulenin, triclosan, diazoborine, naphthyridinones, aminopyridines and pyridoindoles. Our search for new FAB inhibitors, using a lacZ reporter cell-based screen, led to several confirmed hits. Culture F92S91, later identified as a Pseudomonas sp. based on 16S profiling, was found to produce two alpha-pyrones (I and II) and three high molecular weight peptides. The pyrones were unstable under acidic conditions, and they were rearranged into a furanone derivative (III). Of these compounds, pyrone I was the most active with MICs (microg/ml) against B. subtilis (1 to approximately 2), MRSA (2 to approximately 4), M. catarrhalis (4) and VRE (2 to approximately 64). Effects on macromolecular synthesis and membrane functions were tested in B. subtilis. Pyrone I nonspecifically inhibited incorporation of radiolabeled precursors into DNA, RNA and protein within 5 minutes of drug exposure, similar to that of triclosan. Both compounds also inhibited the cellular uptake of these precursors. Cerulenin did not have an effect until 30 minutes of drug treatment. Pyrone I and triclosan were membrane-active (BacLight test); however, pyrone I (at < or = 128 microg/ml concentration) was not hemolytic to human RBCs in contrast to triclosan, which was hemolytic at 16 microg/ml. These data suggest that pyrone-I, unlike triclosan, selectively affects bacterial membrane function.

Bacillus subtilis↗

Cerebrovascular event, dilated cardiomyopathy, and pheochromocytoma.

Cerebral infarction in children may be the result of various disease processes, including emboli from intracardiac sources, paradoxical emboli from the venous system, sickle cell disease, cyanotic heart disease, vasculitis affecting the carotid or cerebral vascular system, vascular anomalies, and prothrombotic states. We present a previously healthy adolescent who presented with the acute onset of hemiparesis. Work-up revealed a dilated cardiomyopathy with a left ventricular mural thrombus as the etiology of his cerebrovascular event. Although dilated cardiomyopathy (DCM) may predispose to the development of a mural thrombus and subsequent embolic events, there are no previous reports in pediatric-aged patients of the development of an embolic event as the presenting manifestation of DCM. Further investigation of the etiology of the DCM led to the diagnosis of a pheochromocytoma. Congestive heart failure and DCM as the presenting sign of pheochromocytoma has likewise not been reported in a pediatric-aged patient. We review this unlikely sequence of events, the diagnostic evaluation of such patients, and treatment options.

Adolescent↗