ABSTRACT
The fungal strain INA 01108 producing antibiotic substances with broad spectrum of antibacterial activity was isolated from the natural environment. By the morphological characteristics and DNA analysis it was shown to belong to Ascomycetes of Sordariomycetes. In submerged culture the strain produced at least four antibiotics. The major component of them was identified as eremophilane-type sesquiterpene eremoxylarin A. Eremoxylarin A is effective in vitro against grampositive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin group glycopeptide antibiotics resistant Leuconostoc mesenteroides VKPM B-4177. The efficacy and toxicity of eremoxylarin A was determined on a murine staphylococcal sepsis model. The dose of 6.25 mg/kg provided 100% recovery and survival of the animals, while the dose of 3.12 mg/kg was close to the ED50. The chemical structure of eremoxylarin A allows to modify the antibiotic and such studies may be relevant to design a less toxic derivative without loss of the valuable antimicrobial properties.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Ascomycota/growth & development , Leuconostoc/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Sepsis/drug therapy , Sesquiterpenes/therapeutic use , Staphylococcal Infections/drug therapy , Animals , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/toxicity , Ascomycota/metabolism , Ascomycota/ultrastructure , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Resistance, Bacterial/drug effects , Mice , Microbial Sensitivity Tests , Polycyclic Sesquiterpenes , Sepsis/microbiology , Sesquiterpenes/isolation & purification , Sesquiterpenes/toxicity , Staphylococcal Infections/microbiologyABSTRACT
Searches for the natural compounds that determine the anticarcinogenic properties of a cruciferous-vegetable diet, revealed the products of alkaloid glucobrassicin biotransformations; among these, ascorbigen, an indole-containing derivative of L-ascorbic acid, was found to be the most abundant. Study of chemical properties of ascorbigen showed that it is capable of different transformations in acidic (including gastric juice) and slightly alkaline (including blood) media. The stable and unstable products of ascorbigen transformation determine the biological properties of the compound. The most important product of ascorbigen transformation in gastric juice is 5,11-dihydroindolo[3,2-b]-carbazole, with a binding affinity to the Ah receptor only 3.7 x 10(-2) lower than that of tetrachlorodibenzodioxin. This compound may be responsible for modifying P450 enzyme activities. Ascorbigen and its analogs are available synthetically. Their biological evaluation showed that some of the compounds of these series are immunomodulators. The most active is N-methylascorbigen, which demonstrates therapeutic effects (inhibition of tumor growth, protection of animals from bacterial and viral infections). The immunomodulatory activity of natural ascorbigen may be an additional factor of importance for the anticarcinogenic properties of a cruciferous-vegetable diet.