Antibiotic Potential of the Ambigol Cyanobacterial Natural Product Class and Simplified Synthetic Analogs

• DOI: 10.1021/acsinfecdis.3c00232
• Publication Date: 2023-09-01T11:35:32Z
• Authors: Tobias M. Milzarek; Milena Stevanovic; Dusan Milivojevic; Sandra Vojnovic; Denis Iliasov; Diana Wolf; Thorsten Mascher; Jasmina Nikodinov...; Tobias A. M. Gulder
• Keywords: triclosan; ambigols; cell membrane integrity; identification; acid; in-vitro; drug-resistant staphylococcus aureus; bacillus-subtilis; antibiotic screening; drug-resistant Staphylococcus aureus; 3. Good health

The ambigols are cyanobacterial natural products characterized by three polychlorinated aromatic building blocks connected by biaryl and biaryl ether bridges. All ambigols known to date possess promising biological activities. Most significantly, ambigol A was reported to have antibacterial activity against Gram-positive bacteria, such as Bacillus megaterium and B. subtilis. We established a diverse compound library for in-depth biological evaluation building on our previous bio- and total synthetic research on this natural product family. To explore the antimicrobial potential in detail and to determine initial structure-activity relationships of this product class, a large set of dimeric and trimeric compounds were screened against selected bacterial and Candida target strains. Our results reveal exceptional antibiotic activity of the ambigols, especially against challenging clinical isolates.