HMG-CoA reductase inhibitor from the endophytic fungus Colletotrichum Capsici

Two new fungal polyketides with unusual skeleton, collecapsins A and B (1-2), along with two known macrolactins A and B (3-4), were isolated from the rice cultures of an endophytic fungus Colletotrichum capsici obtained from the fresh Siegesbeckia pubescens Makino. Their structures were established by a combination of NMR, HRESIMS, and IR analysis. The absolute configurations of 1 and 2 were determined on the detailed analysis of the modified Mosher's derivatives' spectra and its key NOEs correlations. In this case, the absolute configurations of all chiral centres of 1 were determined for the first time, showed that 1 is a C-6/C-8 epimer of colletruncoic acid methyl ester. Compounds 1-2 demonstrated promising lipid lowing activity via the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase with IC₅₀ values of 8.72 and 15.28 μM. Compounds 3-4 exhibited antibacterial activity with MIC values ranging from 0.25-25.8 μM.