| Summary: | The antimicrobial activity of the marine bisindole alkaloid 2,2-bis(6-bromo-3-indolyl) ethylamine (<b>1</b>) and related synthetic analogues (compounds <b>2</b>⁻<b>8</b>) against target microorganisms was investigated by Minimum Inhibitory Concentration (MIC) determination. Compound <b>1</b> showed the greatest antimicrobial activity with the lowest MIC (8 mg/L) against <i>Escherichia coli</i>, <i>Staphylococcus aureus</i>, and <i>Klebsiella pneumoniae</i>, while the derivatives exhibited higher MICs values (from 16 to 128 mg/L). Compounds <b>1</b>, <b>3</b>, <b>4</b>, and <b>8</b>, the most active ones, were then tested against <i>E. coli</i>, <i>S. aureus</i>, <i>K. pneumoniae</i>, and <i>Candida albicans</i> during biofilms formation as well as on 24 h developed biofilms. The natural alkaloid <b>1</b> inhibited the biofilm formation of all the tested microorganisms up to 82.2% and disaggregated biofilms of <i>E. coli</i>, <i>S. aureus</i>, <i>K. pneumoniae</i>, and <i>C. albicans</i> after 30 min of contact, as assessed by viable plate count and crystal violet (CV) staining (optical density at 570 nm). Synthetic derivatives <b>3</b>, <b>4</b>, and <b>8</b> displayed anti-biofilm activity toward individual bacterial populations. This study highlights the potential of marine bisindole alkaloid <b>1</b> as anti-biofilm agent and shows, through a preliminary structure activity relationship (SAR), the importance of halogens and ethylamine side chain for the antimicrobial and antibiofilm activities of this bisindole series.
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