Marine Alkaloid 2,2-Bis(6-bromo-3-indolyl) Ethylamine and Its Synthetic Derivatives Inhibit Microbial Biofilms Formation and Disaggregate Developed Biofilms.

The antimicrobial activity of the marine bisindole alkaloid 2,2-bis(6-bromo-3-indolyl) ethylamine () and related synthetic analogues (compounds ⁻) against target microorganisms was investigated by Minimum Inhibitory Concentration (MIC) determination. Compound showed the greatest antimicrobial activity with the lowest MIC (8 mg/L) against , , and , while the derivatives exhibited higher MICs values (from 16 to 128 mg/L). Compounds , , , and , the most active ones, were then tested against , , , and during biofilms formation as well as on 24 h developed biofilms. The natural alkaloid inhibited the biofilm formation of all the tested microorganisms up to 82.2% and disaggregated biofilms of , , , and after 30 min of contact, as assessed by viable plate count and crystal violet (CV) staining (optical density at 570 nm). Synthetic derivatives , , and displayed anti-biofilm activity toward individual bacterial populations. This study highlights the potential of marine bisindole alkaloid 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.