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Biomedical subjects

G L Neil

Publications and source records attributed to G L Neil.

At least 37 records · Page 2Linked to original sources
PubMed1975

ara-Cytidine acylates. Use of drug design predictors in structure-activity relationship correlation.

This manuscript if one of a series of investigations into modifying the pharmacologic properties of the antitumor, antiviral, and immunosuppressive nucleoside ara-cytidine (cytarabine, Cytosar). The present paper summarizes our studies on depot ester derivatives of the nucleoside. We are able to predict with reasonable accuracy the biological activity as measured by increased life span in the L1210 leukemic mouse from a combination of two predictor variables: (1) the solubility of the ester in water and (2) its rate of hydrolysis by the mixed esterase system of animal plasma. We have tried unsuccessfully to correlate enzymatic hydrolysis rates with an alkaline hydrolysis model. Calculated Hansch partition (p) values had a correlation of r equal to 0.86 with water solubility. These p values had no additional predictive value. Based on our results, two esters were selected for clinical trial in cancer and rheumatoid arthritis.

Acylation↗
PubMed1975

Varicella-zoster virus and subcutaneous cytarabine: correlation of in vitro sensitivities to blood levels.

The susceptibility of 26 strains of varicella-zoster virus to cytarabine was tested in vitro by measuring reduction in number and size of plaques using human foreskin fibroblast cells. Most strains showed 50% reduction of plaque number by 0.125 mug of cytarabine per ml or less. Cytarabine levels in sera of 12 patients after a single subcutaneous injection of 50 mg/M(2) exceeded this inhibitory level for a period of 75 min. Thus, the subcutaneous route is a potentially useful method of administration of cytarabine for antiviral drug trials.

Cytarabine↗
PubMed1974

Inhibition by streptovaricins of Rauscher leukemia virus splenomegaly.

Streptovaricins (Sv), ansa macrolide antibiotics, inhibited Rauscher leukemia virus (RLV) splenomegaly by 25-50%. All streptovaricins tested were effective when administered orally either by diet ad lib or by intubation from infection to time of killing. When delivered by intubation, Sv was measurable in plasma for up to 6 h. SvC, at 300 mg/kg/day, reduced mean spleen weight of infected mice from 478 plus or minus 51 (SE) mg to 300 plus or minus 55 (SE) mg. Rifampicin, at 250 mg/kg/day, had no similar activity. Decrease in caloric intake and in body-weight gain also resulted in an inhibition of RLV splenomegaly; although Sv-treated mice gained weight, the increase was usually slightly less than controls. However, mice treated with a Sv diet for a week prior to infection, after an initial period of weight loss, gained at a rate equivalent to control group, and when killed had a marked reduction in splenomegaly. The selectivity of streptovaricins and specificity for viral events was suggested by several observations: (1) Splenomegaly and mortality, induced by L1210 or a non-infective transplantable tumor of RLV origin, was not inhibited. (2) No inhibition of normal hematopoietic spleen colonies was observed. (3) Host immune responses, including cellular and humoral immunity and interferon production and action, were not inhibited. Thus, although the effect of slightly decreased weight and intake could not be unequivocally established, the findings were most compatible with a selective inhibition of RLV splenomegaly by Sv.

Animals↗