torek, 10. april 2018 Vabilo na predavanje gostov iz Martin-Luther University Halle-Wittenberg
Oddelek za aplikativno naravoslovje UP FAMNIT
vabi na seminar,
ki ga bosta oblikovala dr. Fidele Ntie-Kang in Lucas Praetorius
z Institute of Pharmacy, Martin-Luther University Halle-Wittenberg (Nemčija),
v četrtek 12. 4. 2018, ob 12.00, v predavalnici FAMNIT-Pošta.
Predavanji bosta v angleškem jeziku.
12:00–12:30
Dr. Fidele Ntie-Kang: »African Medicinal Plants: Natural Product Database Development, Lead Discovery and Toxicity Assessment«
Abstract: Within the last two decades, drug discovery based on natural products was almost considered as old fashioned, as combinatorial chemistry quickly took the centre of the stage. However, the decades of combinatorial chemistry, coupled with high throughput screening facilities did not deliver the expected outcomes in terms of new chemical entities and drug approvals. There seems to be a renewed interest in natural product-based discovery, as increasingly new tools are being developed in order to accelerate natural product dereplication and lead discovery, assisted by molecular modeling. The work presented in this thesis focuses on new natural product database tools and datasets for the discovery of lead compounds from African floral matter. Prior to the investigations, data regarding compounds which had been identified from the aforementioned sources were scattered in literature sources, some of which were inaccessible to the wider community of scientists. The resulting investigation has led to a collection of data on the constituent metabolites, their biological activities, as well as the uses of the source organisms in traditional medicine, which have been made available via the web. Moreover, the investigations have led to the identification (assisted and non assisted by molecular modeling) of lead compounds with anti-HIV, anti-Onchocerca, antiplasmodial, protease inhibitory and sirtuin inhibitory properties, beginning from plants with popular uses in African traditional medicine. In parallel, the natural product-inspired discovery of antiplasmodial and sigma-binding new chemical entities has been described. Another aspect of the investigations involved the prediction of the drug metabolism and pharmacokinetics of the secondary metabolites, as well as an overall toxicity assessment of the compounds and databases developed, including the development of a new knowledge base for toxicity prediction. The results presented in this thesis constitute the first outcome of computer-based investigation of the potential of African medicinal plants for drug discovery.
12:30–13:00
Lucas Praetorius: »Structure-guided Screening and Optimization to Design Isoform Selective HDAC Inhibitors«
Abstract: Histone deacetylases (HDAC) are a class of enzymes whose activity is up-regulated in many types of cancer. HDAC inhibitors (HDACi) are successfully used as drugs for the treatment of several types of tumors. So far, all approved HDACi are pan or class-selective inhibitors and therefore show cross-reactivity, toxicity, and at the end unwanted side effects1. To address this issue, we focused on the application of computer- and structure-based approaches (docking studies, analyzing binding data, homology modeling, molecular dynamics studies) to identify novel isoform selective inhibitors. In the current study, we focused on the most-studied isoform HDAC8 as well as on the two least studied isoforms HDAC10 and HDAC11.
Kontaktna oseba:
Prof. Dušanka Janežič (dusanka.janezic@upr.si)
