Lovastatin analogues and other metabolites from soil-derived Aspergillus terreus YIM PH30711

Abstract

Eight previously undescribed metabolites including of lovastatin analogues, a pair of diastereoisomers, a cyclopentenone dimer, and three polyketides were isolated from the culture of Aspergillus terreus YIM PH30711. Two types of unprecedented skeletons, benzene-cyclopentanone complex and linear polyketide, and an unusual dimer structure were determined by spectral analysis. Compound, 3α-hydroxy-3,5-dihydromonacolin L showed moderate activity against HMG-CoA reductase, with an inhibition ratio of 34% at the concentration of 50 μM, while lovastatin and dihydromonacolin K ethyl ester presented much stronger activity against HMGR with inhibition rates of 85% and 90% at the concentration of 50 μM, respectively. Aspereusin A was active against AChE with a ratio of 62% at the concentration of 50 μM, while its stereomers did not showed obvious inhibition (<10%). The configuration at C-4 of these three diastereoisomers was crucial in the inhibition against AChE, and the β-orientation of substituted methoxyl acrylic acid should be beneficial to the combining with AChE.