Executive Summary : | Bacteria have developed resistance to most antibiotics, necessitating the development of new antibacterial agents with novel mechanisms of action. Lipopeptide antibiotics, such as colistin and daptomycin, have shown promising efficacy but are currently used as last resort due to their structural complexity, toxicity, and stability. This proposal aims to design a new class of lipopeptide mimics with potent antibacterial efficacy, overcoming these limitations. The design incorporates lipophilic groups through an aliphatic amine, while amino acids introduce charges. The amino acid side chain also contributes to hydrophobicity. A library of compounds will be prepared by varying aliphatic amines and amino acids, using a simple synthetic strategy based on solution phase chemistry. After successful synthesis and characterization, the antibacterial efficacy of the library will be evaluated through a series of experiments. The antibacterial activity of the entire library will be tested using MIC experiments, followed by toxicity against human red blood cells (hRBCs). A structure-activity-relationship analysis will be performed, identifying at least two to three lead compounds for further development. |