Find in Library

Peptoids are peptidomimetics that have attracted considerable interest as a promising class of antimicrobials against multi-drug-resistant bacteria due to their resistance to proteolysis, bioavailability, and thermal stability compared to their corresponding peptides. <i>Staphylococcus aureus</i> is a significant contributor to infections worldwide and is a major pathogen in ocular infections (keratitis). <i>S. aureus</i> infections can be challenging to control and treat due to the development of multiple antibiotic resistance. This work describes short cationic peptoids with activity against <i>S. aureus</i> strains from keratitis. The peptoids were synthesized via acid amine-coupling between naphthyl-indole amine or naphthyl-phenyl amine with different amino acids to produce primary amines (series <b>I</b>), mono-guanidines (series <b>II</b>), tertiary amine salts (series <b>III</b>), quaternary ammonium salts (series <b>IV</b>), and di-guanidine (series <b>V</b>) peptoids. The antimicrobial activity of the peptoids was compared with ciprofloxacin, an antibiotic that is commonly used to treat keratitis. All new compounds were active against <i>Staphylococcus aureus S.aureus</i> 38. The most active compounds against S.aur38 were <b>20a</b> and <b>22</b> with MIC = 3.9 μg mL⁻¹ and 5.5 μg mL⁻¹, respectively. The potency of these two active molecules was investigated against 12 <i>S. aureus</i> strains that were isolated from microbial keratitis. Compounds <b>20a</b> and <b>22</b> were active against 12 strains with MIC = 3.2 μg mL⁻¹ and 2.1 μg mL⁻¹, respectively. There were two strains that were resistant to ciprofloxacin (<i>Sa.</i>111 and <i>Sa.</i>112) with MIC = 128 μg mL⁻¹ and 256 μg mL⁻¹, respectively. Compounds <b>12c</b> and <b>13c</b> were the most active against <i>E. coli</i>, with MIC > 12 μg mL⁻¹. Cytoplasmic membrane permeability studies suggested that depolarization and disruption of the bacterial cell membrane could be a possible mechanism for antibacterial activity and the hemolysis studies toward horse red blood cells showed that the potent compounds are non-toxic at up to 50 μg mL⁻¹.