Butenolide Derivatives Isolated From Marine Fungus Aspergillus Terreus And Their Pharmacological Avtivities

Lacking of efficient physical protection in the highly competitive living environment, the marine invertebrates including sponges, corals and sea hares. mainly rely on chemical defensive system to survive. Studies have found that there are a lot of associated microorganisms living with marine invertebrates, and these microorganisms may be involved in the chemical defence of the host through producing a series of secondary metabolites with antimicrobic, antifouling or toxic activities. Butenolides with potent bioactivities are one of these common secondary metabolites of marine invertebrates or the associated microorganisms.In previous studies a series of butenolides with strong antifouling activity were isolated from marine fungus Aspergillus terreus. In this dissertation. Using butyrolactone I as internal standard, several fermentation conditions of the fugus were designed to raise productivity of butenolides. The fugus grew rapidly in rice culture medium and produced more butenolides. Four butenolides (1-4) and a terrein (5) were isolated from A. terreus, and the structural modification gave four derivatives of compound 1. The mycrobacterium tuberculosis protein tyrosine phosphatase B (MPtpB) inhibitory activity was designed and used to value the bioactivity of compound 1 and its derivatives. Compound 1 showed potent MPtpB inhibitory activity, but when the hydroxy groups were acetylated the MPtpB inhibitory activity decreased. The molecular docking result indicated that the lactone group play an important role in binding with the active pocket of MPtpB. The other pharmacological activities’data showed that all butenolides showed selective antiviral activity with low therapeutic ratio, but only compound 5 showed week cytotoxic activity to all tested human cancer cell lines.In conclusion, butenolide compound 1 showed great bioactivity and lead to the discovery of a better fermentation condition of A. terreus to produce more butenolides. This research supply important clue to find lead compounds in drugs discovery.