Effects of Secondary\nAmine and Molecular Weight on\nthe Biological Activities of Cationic Amphipathic Antimicrobial Macromolecules

Cationic amphipathic antimicrobial agents inspired by\nantimicrobial\npeptides (AMPs) have shown potential in combating multidrug-resistant\nbacteria because of minimal resistance development. Here, this study\nfocuses on the development of novel cationic amphipathic macromolecules\nin the form of dendrons and polymers with different molecular weights\nthat employ secondary amine piperidine derivative as the cationic\nmoiety. Generally, secondary amine compounds, especially at low molecular\nweights, have stronger bacteriostatic, bactericidal, and inner membrane\ndisruption abilities than those of their primary amine counterparts.\nLow molecular weight <b>D2</b> dendrons with two cationic centers\nand one hydrophobic dodecyl chain produce outstanding synergistic\nactivity with the antibiotic rifampicin against <i>Escherichia\ncoli</i>, where one-eighth of the standalone dose of <b>D2</b> dendrons could reduce the concentration of rifampicin required by\nup to 4000-fold. The low molecular weight compounds are also less\ntoxic and therefore have higher therapeutic index values compared\nto compounds with larger molecular weights. This study thus reveals\nkey information that may inform the design of future synthetic AMPs\nand mimics, specifically, the design of low-molecular-weight compounds\nwith secondary amine as the cationic center to achieve high antimicrobial\npotency and biocompatibility.