Amelia Pilar Rauter
University of Lisbon, Portugal
Title: Glycan synthesis towards new glycolipid antibiotics with new mechanisms of action
Biography
Biography: Amelia Pilar Rauter
Abstract
The search for new antimicrobial drugs is currently one of the major ongoing research areas due to the spread of multidrug-resistance, thus encouraging research on antibacterial agents with new mechanisms of action. A new family of antibiotics, structurally based on glycolipids, with a potent antimicrobial activity against Bacillus species will be disclosed. We present our recent findings that cover synthetic approaches to new antimicrobial molecular entities differing in the glycon structure, based on alkyl deoxy pento- and hexopyranosides belonging to the D- or L-series. Stereochemistry, in particular the anomeric configuration, and the deoxygenation pattern are modified in order to evaluate their contribution to the structure/activity relationship. Also the lipophilic chain is changed for the recognition of the key structural features for the bioactivity/selectivity for Bacillus species. The surface properties of the most active compounds, in terms of adsorption and aggregation parameters, are also presented. Although surface activity is required for the bioactivity, this property is not sufficient to account for bioactivity, as shown by some promising surface active glycosides, that were not active. In order to have insights into the mechanism of action of this family of compounds, expected to target bacterial membranes, a multidisciplinary approach covering biophysical and biological methods was followed. The elucidation of the new mechanisms of action of this family of antibiotics will be disclosed and discussed, demonstrating the relevance of the glycan structure for the bactericidal activity.