• Universitat de València
• Carlos III Health Institute
• Spanish National Research Council
• CIBER on respiratory diseases

• Adela González de la Campa
• María Teresa García Esteban

Strepctococcus pneumoniae, a Gram-positive pathogenic bacterium, is the main aetiological agent of community-acquired pneumonia. Their DNA topology is maintained by DNA topoisomerases of type II (gyrase and Toposiomerase IV) and type I (Top A). Type II are targets for fluoroquinolones. To date, there are no effective inhibitors against TopA. Antimicrobial resistance is a serious clinical and public health problem worldwide. Moreover, the emergence of fluoroquinolone-resistant pneumococci is foreseeable in the future. This calls for a search for new antimicrobials, ideally against new targets.

The invention concerns the use of two phenanthrenic alkaloids, seconeolitsin and N-methylseconeolitsin, in the manufacture of medicines, preferably for the treatment of diseases caused by S. pneumoniae. The invention has been based on the overexpression and purification of DNA topoisomerase I (Top A), the synthesis of 18 aporphinic and phenanthrenic alkaloids derived from the natural alkaloid boldine and the determination of both their antibacterial activity and effect on Top A. In this invention a DNA topoisomerase I from a Gram-positive pathogenic bacterium is characterised for the first time. Both seconeolitsin and N-methyl-sconeolitsin could be used as new antibiotics because of their antimicrobial activity. The efficacy of both compounds has been determined against S. pneumoniae.

For the first time, antibiotics inhibiting DNA topoisomerase I would be put on the market. This means the establishment of a new antimicrobial target.

• High specificity.
• Known mechanism of action.
• There is no known resistance to these compounds.

• Patent granted