One of the major threats of the 21<sup>st</sup> century is the resistance of microorganisms toward medicines, known as antimicrobial resistance (AMR). The bacterial resistance is peculiarly important since most of the announced <i>urgent threats</i> of microorganisms are bacteria. To combat bacterial resistance, the mimics of the natural antimicrobial peptides (AMPs) have been studied through the synthesis of small molecules, macromolecular and dendrimer-like systems over decades. However, those systems suffer the high entropic penalty while arranging their structure at contact with the bacteria membrane. Facial amphiphilicity is an extraordinary feature of a variety of AMPs to battle pathogenic bacteria which reduces the local and global arrangement forfeit. The quantitative analysis of facial amphiphilicity impact on antimicrobial efficacy was lacunary in the literature. This work conceptualizes Facial Amphiphilicity Index (FAI) as a numerical value to quantitatively characterize the measure of structural features in dictating antimicrobial efficacy. Cationic derivatives of multicyclic compounds were evaluated as model systems for testing antimicrobial selectivity against both Gram-negative and Gram-positive bacteria.

Facial amphiphilicity index as a robust structure feature on antimicrobial efficacy

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