Bixiamycines –novel natural compounds with broad-spectrum antibiotic activity
The rise of bacterial resistance against commonly used drugs remains a major challenge to modern medical treatment that continuously constitutes the need for new antibacterial agents. Emerging diseases, e.g. tropical diseases increase said need. Although several new antibiotics have been developed to combat bacterial infections including MRSA, their side effects still leave room for improvements.
Novel natural small molecules isolated from a mangrove endophyte are provided. The new bixiamycins are dimeric indolosesquiterpenes with broad antibacterial activity without relevant cytotoxic activity (IC50 and CC50 >30µg/mL). Most of the family members are active against relevant gram-positive and even against gram-negative pathogens such as Pseudomonas aeruginosa. The dimeric molecules are so called rotamers in which steric hindrance of substitutes restricts the occurrence of some rotational angles, a feature that proved to be crucial for the pharmacological effect of bioactive compounds.
The technology is offered for co-development and/or licensing.
The antimicrobial activity profile of the bixiamycins is currently under further investigation. Results from in vitro assays are available. The total chemical synthesis is being elaborated at present.
Priority was filed in August 2012. An international application was filed in 2013 (WO2014029498). European patent application pending.
Baunach et al. Regiodivergent N-C and N-N aryl coupling reactions of indoloterpenes and cycloether formation mediated by a single bacterial flavoenzyme. Angew Chem Int Ed Engl. 2013 Aug 19;52(34):9040-3.