Antimicrobial activity of clavines

Abstract

The antimicrobial activity of two clavine-type ergot alkaloids (agroclavine, festuclavine), and 16 derivatives against four human pathogenic bacteria and Candida albicans was determined. It is shown that all ergolines tested with one exception exhibit antibacterial properties against one to four bacterial species. The most active compounds are 6-allyl-6-norfestuclavine (minimal inhibitory concentration (MIC) 30 μg/ml against Staphylococcus aureus), 1-propyl-6-norfestuclavine (MIC 60 μg/ml against Escherichia coli), 6-cyano-6-norfestuclavine (MIC 250 μg/ml against Pseudomonas aeruginosa), and 1-methyl-agroclavine (MIC 200 μg/ml against Proteus vulgaris). 1-Allyl-6-norfestuclavine and 1-propyl-6-norfestuclavine showed a broad action spectrum: the growth of all four bacterial species and of Candida albicans was inhibited. The most effective antifungal compounds are 1-propyl-6-norfestuclavine and 6-cyano-6-norfestuclavine (MIC 250 μg/ml). Three alkoloids of different structure (codeine, emetine, quinine) are inactive up to 500 μg/ml against the bacteria species and C. albicans. The acute toxicity (mouse) is remarkably diminished by the modifications of the natural clavines.