Lovastatin Analogues from the Soil-Derived Fungus <i>Aspergillus sclerotiorum</i> PSU-RSPG178

Three new lovastatin analogues (<b>1</b>, <b>4</b>, and <b>5</b>) together with four known lovastatin derivatives, namely, lovastatin (<b>2</b>), α,β-dehydrolovastatin (<b>3</b>), α,β-dehydrodihydromonacolin K (<b>6</b>), and α,β-dehydro-4a,5-dihydromonacolin L (<b>7</b>), were isolated from the soil-derived fungus <i>Aspergillus sclerotiorum</i> PSU-RSPG178. Their structures were established using spectroscopic evidence. Compound <b>5</b> exhibited the most potent activity against HMG-CoA reductase, with an IC₅₀ value of 387 μM. In addition, the present study indicated the direct interaction of compound <b>5</b> with HMG-CoA reductase. Compound <b>5</b> was considered to be noncytotoxic against noncancerous Vero cells, with an IC₅₀ value of 40.0 μM, whereas compound <b>2</b> displayed much stronger activity, with an IC₅₀ value of 2.2 μM