Executive Summary : | Antimicrobial resistance is a growing global health concern, necessitating the development of novel anti-microbial agents with a novel mechanism of action. Membrane-targeting antibiotics like Ceragenins have shown promise due to their amphiphilic conformations. A new approach involves synthesizing bile acid-based cyclopeptides, mimicking squalamine and Polymyxin B, which can selectively disrupt microbial membranes. These steroid cyclopeptides are expected to act as synergistic agents with other antibiotics. The synergistic effect of synthesized analogs in combination with other antibiotics will be investigated. In vitro antimicrobial studies will be conducted against gram-positive, gram-negative, and fungal strains. Fluorometric assessment of selective permeabilization of microbial membranes will be conducted using 1-N-phenylnaphthylamine and/or 3,3-diethylthiadICARbocyanine iodide probes. The project will involve detailed structure Activity Relationship studies to identify a new HIT molecule for further development as an antimicrobial or synergistic agent. |