Secondary Metabolites From A Sponge And A Sponge-derived Fungus And Their Microalgal Growth-inhibition Activities

The unique marine environment （high-salted, high-pressured, lucifugal and anoxygenous,etc.） endows the marine organisms with special survival mechanisms, sponge and theirsymbiotic microbes are important source of marine natural products. Secondary metaboliteswith various structures showed significant biological activities, with a broad medicinaldevelopment prospects. It is noteworthy that large number of symbiotic microbes exist insponges，and studies have been focused on these microbes.In this paper, the secondary metabolites of a sponge and a sponge-derived fungus wereinvestigated according to the methods of chromatography （silica gel, Sephadex LH-20, ODSand HPLC） and spectroscopy （NMR, MS, IR, UV）. Compounds isolated from marineorganisms and their symbiotic fungi were evaluated on miniaturized microalgalgrowth-inhibition bioassay, and based on the data from the assay, their structure-activityrelationships were analyzed.Compounds （1-10） were evaluated from sponge Dactylospongia elegans （WMS-18）,including two sesquiterpene tetronic acids （1–2）, two sesquiterpene hydroquinones （3–4）, twosteroids （5–6）. two nucleosides （7–8），and two pyrimidines (9^–10). Sesquiterpene quinonesand related compounds constitute an important class of natural products from spongeDactylospongia elegans. Dactyltronic acids were reported as isomers in previous reports.Compound5, a steroid bearing a double α, β-unsaturated ketone moiety in the B ring, hadalmost been reported from synthesis, which was rare reported from nature previously.Fourteen compounds （11-24） were identified from sponge-derived fungus Penicilliumsp.（LWZ14-1）, including citrinins （11-15）, steroids （16-23）, and polyketones （24）. It wasfound that the main compositions of fungus Penicillium were citrinins. Compound11and12compounds were monomers, along with compound13,14and15were citrinin dimers.Compounds16-22were unusual C25steroid isomers with bicycle [4.4.1] A/B rings, which was rare reported previously.Miniaturized microalgal growth-inhibition bioassay model combined with otherscreening models, including acetylcholinesterase inhibitory activity, and antibacterial wereused to evaluate bioactivities. The results indicated that compound11-13showed moderategrowth-inhibition activity towards microalgae with EC50of20.97μg/mL,18.56μg/mL,8.66μg/mL; Compound16-21showed significant growth-inhibition activity towards microalgaewith EC50values of6⁸μg·mL^–1. Dactyltronic acids （1/2） showed pronounced antibacterialactivity against V. parahemolyticus with an MIC value of3.45μM, pregna-1,20-dien-3-one （6）also exhibited activity toward B. cereus with a MIC value of4.19μM, similar to that of thepositive control ciprofloxacin; Compounds13,14and20respectively showed inhibitionactivity towards acetyl cholinesterase with the IC50value of23μM,0.042μM,0.166Μm.Miniaturized microalgal growth-inhibition activity model was used to evaluate theactivity and toxicity of106secondary metabolites isolated from marine organisms and theirsymbiotic fungus. The analysis of structure-activity relationships indicated thatanthraquinones, biphenylene oxides, sterides, isocoumarins, and citrinins showed significantgrowth-inhibition activity towards microalgae. The indoles, sesquiterpenoid, and nucleosidesshowed week growth-inhibition activity towards microalgae.In conclusion, the isolated secondary metabolites of sponge Dactylospongia elegans andsponge-derived fungus Penicillium sp. have provided compounds foundation forchemotaxonomic studies of marine species, and offered reference for exploring therelationship between the hosts and their symbiotic microbes. Studies on microalgalgrowth-inhibition bioassay and structure-activity relationship of indole alkaloids, biphenyleneoxides, anthraquinones, and isocoumarins have provided basic information for the discussionof structures and functions of marine chemical ecology.