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Biomedical subjects

P Traxler

Publications and source records attributed to P Traxler.

At least 37 records · Page 2Linked to original sources
PubMed1990

Thiazolidine-diones. Biochemical and biological activity of a novel class of tyrosine protein kinase inhibitors.

Various derivatives of thiazolidine-diones have been identified as tyrosine protein kinase inhibitors. The epidermal growth factor (EGF) receptor kinase and c-src kinase were inhibited in vitro with IC50 values in the range of 1-7 microM. The v-abl tyrosine protein kinase was not inhibited by thiazolidine-diones. Inhibition was found to be specific for tyrosine protein kinases. Inhibition of serine/threonine protein kinases was not observed. The active derivatives were shown to inhibit EGF-induced receptor autophosphorylation, either in vitro or in intact cells, and were also found to inhibit growth of the EGF-dependent BALB/MK and A431 cell lines (IC50 1-3 microM). Growth of the interleukin-3-dependent myeloid cell line FDC-P1 was inhibited with equal efficiency. Thus, in these cell lines, members of the c-src kinase family are also potential targets for inhibition by the compounds.

Animals↗
PubMed1990

Hypolipidemic activity of rifamycin derivatives.

Series of 3-piperidinyl- and 3-piperazinylrifamycins and to a certain extent 3-hydrazonorifamycins all bearing lipophilic side chains were found to exert potent hypolipidemic activity in lowering both serum cholesterol and LDL-cholesterol in rats. Starting from 3-[N'-(2,4,6-trimethylbenzyl)-N-piperazinyl]rifamycin SV (compound 25), a series of derivatives were synthesized with the aim of dissociating the hypolipidemic from the antibacterial activity, leading to the 8-O,N-dipivaloyl derivative of 25 (compound 48), which is devoid of any antibacterial activity but shows about 50-60% reduction of LDL-cholesterol and 20-30% reduction of serum cholesterol at a dose of 10 mg/kg. Compound 48 was selected for further pharmacological evaluation.

Animals↗
PubMed1987

Papulacandins--synthesis and biological activity of papulacandin B derivatives.

A series of papulacandin B derivatives was synthesized and their in vitro and in vivo activity against Candida albicans and other fungi was established. The biological data have shown that some 10-alkyl ether and 11-acylamino derivatives exhibit an improved in vivo activity compared to papulacandin B whereas derivatization in other positions of the molecule led to less potent compounds.

Aminoglycosides↗
PubMed1983

Papulacandins--the relationship between chemical structure and effect on glucan synthesis in yeast.

Papulacandin B inhibits glucan biosynthesis in cells of Saccharomyces cerevisiae and Candida albicans. Biological studies with a series of papulacandin derivatives showed that the short fatty acid chain and the galactose residue are not required for activity at the target site, but that they can affect penetration. On the other hand, the long fatty acid residue is essential for biological activity.

Aminoglycosides↗
PubMed1980

Early intermediates in the biosynthesis of ansamycins. III. Isolation and identification of further 8-deoxyansamycins of the rifamycin-type.

A number of minor compounds were isolated from fermentations of the protorifamycin I producing strain Nocardia mediterranei F 1/24(1,2)) and identified by means of chemical and spectroscopic methods. Two types of structures were identified: Type 1: modified protorifamycins (derived from protorifamycin I) Type 2: defective rifamycins (8-deoxyrifamycins).

Anti-Bacterial Agents↗
PubMed1980

Papulacandins, a new family of antibiotics with antifungal activity. Structures of papulacandins A, B, C and D.

The structures of the papulacandins A, B, C and D, new antibiotics of Papularia sphaerosperma have been established by means of spectral analysis and degradation reactions. Base catalysed hydrolysis of the main product papulacandin B (1) gave two new hydroxylated long-chain unsaturated fatty acids 5 and 6 along with a hitherto unknown spirocyclic diglycoside 7. The structure of 7 was determined by further degradation reactions. The positions of attachment of the two fatty acids to the spirocyclic diglycoside 7 through ester-bonds were established by selective base catalysed hydrolysis of 1 and spectral analysis of 1 and some derivatives and degradation products thereof. The structures of papulacandin A (2), papulacandin C (3) and papulacandin D (4) were determined in an analogous way.

Aminoglycosides↗
PubMed1979

Early intermediates in the biosynthesis of ansamycins. II. Isolation and identification of proansamycin B-M1 and protorifamycin i-M1.

Proansamycin B-M1 and protorifamycin I-M1 were isolated as minor compounds from fermentations of the protorifamycin I producing strain Nocardia mediterranei F 1/24, identified by means of chemical and spectroscopic methods and shown to be degradation products of the hypothetical proansamycin B postulated in part I of this series of papers and of protorifamycin I, respectively.

Anti-Bacterial Agents↗
PubMed1977

Papulacandins, a new family of antibiotics with antifungal activity, I. Fermentation, isolation, chemical and biological characterization of papulacandins A, B, C, D and E.

Papulacandin, a new antibiotic complex, active against Candida albicans and several other yeasts, was isolated from a strain of Papularia sphaerosperma. The fermentation, isolation, physico-chemical properties and biological activity of the five structurally related papulacandins A, B, C, D and E are reported. Papulacandin B, the main component, was assigned the formula of C47H64O17.

Animals↗
PubMedDate not supplied

Strategies toward the design of novel and selective protein tyrosine kinase inhibitors.

Protein tyrosine kinases play a fundamental role in signal transduction pathways. Deregulated tyrosine kinase activity has been observed in many proliferative diseases (e.g., cancer, psoriasis, restenosis, etc.). Tyrosine kinases are, therefore, attractive targets for the design of new therapeutic agents against cancer. We have built up a pharmacophore model of the ATP-binding site of the epidermal growth factor receptor (EGFR) kinase and used it for the rational design of kinase inhibitors. Several examples of the successful use of this model are presented in this review. Amongst these, 4-substituted-pyrrolo[2,3-d]pyrimidines, a new class of highly potent and selective inhibitors of the EGFR kinase, have been identified and further optimized. The most active derivatives inhibited the EGFR tyrosine kinase with IC50 values between 1 and 5 nM. In EGF-dependent cellular systems, tyrosine phosphorylation, as well as c-fos mRNA expression, was inhibited with similar IC50 values. Further successful application of this pharmacophore model led to the identification and optimization of phenylamino-pyrazolo[4,3-d]pyrimidines and substituted isoflavones and quinolones, other classes of potent, selective, and ATP competitive EGFR kinase inhibitors with IC50 values in the low nanomolar range. Structure-activity relationships of both classes are discussed.

Adenosine Triphosphate↗