Preliminary experimental and clinical results with a new synthetic emetine-like compound.
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Several new isoquinolines were prepared using Reissert compounds. A few compounds were screened, and they exhibited no antineoplastic activity.
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Derivatization of the alkaloids cephaeline, codeine, emetine, ephedrine, morphine, narcotine and others with dansyl chloride has been studied with the aim of developing a sensitive and specific liquid chromatographic method for these substances in complex pharmaceutical dosage forms. While codeine and narcotine do not react, the other compounds form completely substituted derivatives which possess maxima in their fluorescence emission spectra between 470 and 500 nm. The structure of the derivatives has been confirmed by nuclear magnetic resonance spectroscopy. The dansylated compounds have been separated by thin-layer chromatography and high-pressure liquid chromatography. The improved selectivity and sensitivity have permitted an analysis of these substances present in low concentrations in 10- 100-fold excesses of other drugs. Direct derivatization of syrups and aqueous slurries of capsules having a complex excipient and drug composition is feasible and time saving and serves as a pre-clean-up step. Detection limits are in the 1-10-ng range or better, depending on the efficiency of the detection device. The reproducibility of the method is limited by the derivatization step, but a relative standard deviation of less than 2% can be obtained. The analysis time for these pharmaceuticals may be reduced by at least one fifth of that required by conventional techniques.
The development of an assay to measure the sensitivity of drugs against Blastocystis hominis using the incorporation of 3H-hypoxanthine is described. The activity of 42 compounds have been measured. Four of the 5-nitroimidazoles tested (satranidazole, S75 0400 A, flunidazole and ronidazole) were found to be more active than metronidazole, the drug commonly used to treat infections caused by B. hominis in humans. Other potentially useful compounds include emetine, furazolidone and quinacrine. Ketoconazole and iodoquinol reported to have therapeutic activity in infections caused by this parasite were found to be significantly less active than metronidazole.
Selected natural compounds were evaluated for their effects on dental caries due to different strains of Streptococcus mutans bacteria. Out of 39 tested compounds, four (catechol, emetine, quinine, and flavone) showed potent inhibitory activity on different strains of S. mutans at 6.25 microg/mL or less with inhibition of adherence <50%, two compounds (5,7-dihydroxy-4'-methoxy isoflavone and ellagic acid) exhibited a moderate inhibitory effect at 12.5 microg/mL with inhibition to adherence <50%, and 12 compounds exhibited weak antibacterial activity at 125 microg/mL or more with inhibition of adherence <25%. These compounds represent three major classes of natural products: tannins, alkaloids, and flavonoids. Further study for possible application of these compounds as inhibitors for dental caries is underway.
Studies on the binding spectra of certain alkaloids with rat liver microsomes revealed that brucine, scopolamine and strychnine are type I compounds, whereas boldine, emetine, nicotine, reserpine and sanguinarine show type II binding. In contrast, colchicine and solanine failed to produce any measurable binding spectra. In vitro incubation of colchicine, nicotine or scopolamine with microsomal suspensions and NADPH resulted in demethylation of these alkaloids, while the incubation of boldine, brucine, emetine, reserpine, sanguinarine or solanine showed little or no dealkylation reaction. Furthermore, the effect of these alkaloids on the in vitro microsomal metabolism of a drug, benzphetamine, has also been studied.