Harald Greger

Bio: Harald Greger is an academic researcher from University of Vienna. The author has contributed to research in topics: Glycosmis & Stemona. The author has an hindex of 37, co-authored 157 publications receiving 4864 citations.

Testing of antifungal natural products: methodologies, comparability of results and assay choice

Abstract: Antifungal testing of filamentous fungi generally suffers from incomparability of results. In order to illustrate this problem, the polyacetylene falcarindiol and the naphthoquinone juglone, two known antifungal natural products, were assayed in various dilution and diffusion bioassays against three selected microfungi, Botrytis cinerea, Cladosporium herbarum and Fusarium avenaceum. Broth microdilution, based on the 96-well microtitre plate format, can be scored by various direct and biochemical methods. As examples, direct observation with image analysis and the fluorescein diacetate scoring method are compared. Of the other methodologies used, results obtained by thin-layer bioautography and the radial growth rate method clearly deviated. Disk diffusion results, however, matched microdilution. In conclusion, microdilution offers the greatest potential of all bioassays to become the future general standard methodology. Copyright © 2000 John Wiley & Sons, Ltd.

Therapeutic suppression of translation initiation modulates chemosensitivity in a mouse lymphoma model.

Abstract: Disablement of cell death programs in cancer cells contributes to drug resistance and in some cases has been associated with altered translational control. As eukaryotic translation initiation factor 4E (eIF4E) cooperates with c-Myc during lymphomagenesis, induces drug resistance, and is a genetic modifier of the rapamycin response, we have investigated the effect of dysregulation of the ribosome recruitment phase of translation initiation on tumor progression and chemosensitivity. eIF4E is a subunit of eIF4F, a complex that stimulates ribosome recruitment during translation initiation by delivering the DEAD-box RNA helicase eIF4A to the 5′ end of mRNAs. eIF4A is thought to prepare a ribosome landing pad on mRNA templates for incoming 40S ribosomes (and associated factors). Using small molecule screening, we found that cyclopenta[b]benzofuran flavaglines, a class of natural products, modulate eIF4A activity and inhibit translation initiation. One member of this class of compounds, silvestrol, was able to enhance chemosensitivity in a mouse lymphoma model in which carcinogenesis is driven by phosphatase and tensin homolog (PTEN) inactivation or elevated eIF4E levels. These results establish that targeting translation initiation can restore drug sensitivity in vivo and provide an approach to modulating chemosensitivity.

Antitumor activity and mechanism of action of the cyclopenta[b]benzofuran, silvestrol.

Abstract: Canadian Institutes of Health Research (16512, Cancer Consortium Training Grant Award, CancerConsortium Training Grant Award); US Lymphoma Foundation Award; National Institute of Health (RO1 GM073855); National Crime Information Center (017099); Cole Foundation Award

Structural Relationships, Distribution and Biological Activities of Stemona Alkaloids

Abstract: Stemona alkaloids represent a unique class of natural products exclusively isolated from the monocotyledonous family Stemonaceae comprising three genera mainly distributed in southeast Asia Structurally the alkaloids are characterised by a pyrrolo[1,2- a]azepine nucleus usually linked with two carbon chains mostly forming terminal lactone rings Based on biosynthetic considerations and their various distribution the present review describes 82 Stemona alkaloids grouped into three skeletal types Due to different carbon chains attached to C-9 of the pyrroloazepine nucleus they were classified into stichoneurine-, protostemonine- and croomine-type alkaloids The genera Croomia and Stichoneuron only accumulate croomine or stichoneurine derivatives, respectively, whereas the genus Stemona produces all three types of alkaloids However, species-specific accumulation trends towards certain structural types represent valuable chemosystematic criteria Bioassays with larvae of Spodoptera littoralis exhibited very high insect toxicity for the roots of Stemona species containing certain protostemonine derivatives, especially didehydrostemofoline, whereas those with dominating stichoneurine or croomine derivatives showed low toxicity but sometimes remarkable repellence due to an accumulation of tuberostemonine Tuberostemonine also showed effects on the motility of helminth worms and reduced the excitatory transmission at the crayfish neuromuscular junction Significant antitussive activity was shown for the stereoisomeric neotuberostemonine in guinea-pig after cough induction by citric acid aerosol stimulation Studies on structure-activity relationship with seven related compounds revealed that the saturated tricyclic pyrrolobenzazepine nucleus of tuberostemonines is the prerequisite for antitussive activity

In vitro inhibition of cyclooxygenase and 5-lipoxygenase by alkamides from Echinacea and Achillea species.

Abstract: Polyunsaturated alkamides isolated from Achillea species, Echinacea angustifolia DC., Anacyclus pyrethrum (L.) Link, and Aaronsohnia pubescens (Desf.) Bremer & Humphries, (Compositae) were shown to possess inhibitory activity in in vitro cyclooxygenase (sheep seminal microsomes) and 5-lipoxygenase (porcine leukocytes) assays. Activity appeared to depend on the particular structure of the alkamides.

Translational control in cancer.

Abstract: Remarkable progress has been made in defining a new understanding of the role of mRNA translation and protein synthesis in human cancer. Translational control is a crucial component of cancer development and progression, directing both global control of protein synthesis and selective translation of specific mRNAs that promote tumour cell survival, angiogenesis, transformation, invasion and metastasis. Translational control of cancer is multifaceted, involving alterations in translation factor levels and activities unique to different types of cancers, disease stages and the tumour microenvironment. Several clinical efforts are underway to target specific components of the translation apparatus or unique mRNA translation elements for cancer therapeutics.