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R Kasper

Publications and source records attributed to R Kasper.

6 recordsLinked to original sources
PubMed1994

Biotransformation of the naturally occurring lignan (-)-arctigenin in mammalian cell lines genetically engineered for expression of single cytochrome P450 isoforms.

V79 Chinese hamster cells genetically engineered for stable expression of single forms of rat cytochromes P450 1A1, P450 1A2, and P450 2B1, and human P450 1A2 were used to analyse the metabolism of (-)-arctigenin. Concentrations of metabolites formed in the medium were determined by TLC, HPLC, GC, and GC-MS. Only in the cell line expressing rat P450 2B1 was (-)-arctigenin metabolized to a significant extent. The lignan was converted by O-demethylation to (-)-3'-O-demethylarctigenin.

Animals↗
PubMed1992

Clavine alkaloids and derivatives as mutagens detected in the Ames test.

Eight cytostatic clavines were investigated for mutagenicity in Salmonella typhimurium (reversion of the his-strains TA98, TA100, TA102 and TA1537), directly and in the presence of a mammalian xenobiotic metabolizing system, S9 (NADPH-fortified postmitochondrial fraction of liver homogenate from Aroclor 1254-treated rats). Four compounds (festuclavine, 17-bromofestuclavine, 1-allylelymoclavine and 1-methyllysergol methyl ether) were direct mutagens, whose activity was enhanced in the presence of S9. The other compounds (1-cyclopentylfestuclavine, 13-bromo-1-cyclopropylmethylfestuclavine, 6-cyano-1-propyl-6-norfestuclavine and 6-allyl-1-propyl-6-norfestuclavine) showed mutagenic effects only in the presence of S9, as previously observed with other clavines (agroclavine and its 1-propyl and 1-pentyl derivatives). Thus, all investigated clavines may be metabolized to mutagenic products by mammalian enzymes. Bacteriotoxic activities did not correlate with mutagenic activities. The bacteriotoxicity of several clavines was reduced in the presence of S9. The results are discussed with regard to the potential therapeutic use of clavine alkaloids as antimicrobial and antineoplastic agents.

Animals↗
PubMed1990

Inhibitory effects of novel festuclavine derivatives on nucleoside uptake and incorporation into DNA and RNA in human lymphoid leukemia Molt 4B cells.

Effects of festuclavine derivatives on nucleoside uptake by human lymphoid leukemia Molt 4B cells and on incorporation into TCA-insoluble materials in the cells were examined. The uptake and incorporation of uridine or thymidine were suppressed by festuclavine (EN01), 13-bromo-1-cyclopropylmethyl-festuclavine (EN02), 1-(4-chloro-benzenesulfonyl)festuclavine (EN03) and 1-cyclopentyl festuclavine (EN04) at 10-50 microM. Among these compounds, EN02 was most effective and at 50 microM it completely suppressed cellular uptake of the nucleosides and their incorporation into TCA-insoluble materials inhibiting the cellular proliferation. EN03 and EN04 moderately inhibited the transport and incorporation of the nucleosides in dose-dependent manners, while the mother compound EN01 had the least inhibitory effect. These findings indicated that alkylation at the indole nitrogen in combination with bromination at C-13 of the festuclavine molecule strengthened its inhibitory action on nucleoside uptake to a remarkable extent. The inhibition curves of nucleoside incorporation into TCA-insoluble materials showed quite similar dose-dependence to those of the inhibition curves for cellular nucleoside transport. These results suggest that the inhibitions of DNA and RNA syntheses by the festuclavine derivatives are due to the depressed transport of nucleosides into the leukemia cells.

Antibiotics, Antineoplastic↗
PubMed1984

Persistent perineal sinus.

Perineal sinus, the most common late complication following proctectomy, is of major morbidity to the patient; the wound can be incapacitating to the patient and refractory to ordinary treatment. Various surgical procedures are detailed.

Female↗