GluMi
New glutaminyl cyclase inhibitors from marine microalgae and other natural sources as drug candidates for the treatment of periodontitis
The aim of the project is the evaluation of substances from marine microalgae and from mosses and liverworts as potential inhibitory pharmaceuticals. Of particular interest are glutaminyl cyclase inhibitory compounds isolated from the lipid fraction of selected marine microalgae species, which belong to classes that have not been studied previously in this respect, i.e. diatoms (Bacillariophyta) and Eustigmatophyceae (Ochrophyta). Cultivation of some of these species is challenging and still being explored, but is crucial as the generation of sufficient algal biomass is a prerequisite for detailed analysis of active compounds and even more for future biotechnological production of algal extracts for phytopharmaceuticals.
Glutaminyl cyclases (QC/iso-QC) are current drug targets for the treatment of neurodegenerative and inflammatory disorders, and cancer. A first QC inhibitor PQ912 is currently undergoing a phase 2b clinical study in Alzheimer’s disease. Moreover, QCs have been discovered in pathogenic bacteria of the “red complex”, which cause periodontitis. Hence, inhibitors of QC are potential future drugs for treatment of various disorders. The present project focuses on a proof of concept for inhibition of QCs by natural products and their derivatives in models of periodontitis and bacterial infection by periodontal pathogens. Besides algae, mosses and liverworts are to be included in the investigations with regard to QC inhibition and further yet unknown inhibitory mechanisms, as these have shown an inhibitory effect on the periodontal pathogen Porphyromonas gingivalis in preliminary experiments.
