In the early stage of atherosclerogenesis, macrophages penetrate the
intima, efficiently take up modified low-density lipoprotein, store
cholesterol and fatty acid as a respective form of cholesteryl ester (CE)
and triacylglycerol (TG) in cytosolic lipid droplets, and are converted
into foam cells, leading to the development of atherosclerosis in the
arterial wall. Therefore, inhibition of lipid droplet accumulation in
macrophages would be expected to retard the progression of atherosclerosis.1–4
In the course of our screening program for microbial inhibitors of
lipid droplet formation in mouse macrophages,5–10 three new compounds
designated pentacecilides A to C (Figure 1), structurally
related to known thailandolides A and B,11 were isolated from the
culture broth of a soil-isolated fungus, FKI-3765-1. Thailandolides
were originally isolated as fungal metabolites from Talaromyces
thailandiasis,
11 and were not isolated from the culture broth of strain
FKI-3765-1. Pentacecilides A and B were found to inhibit lipid droplet
formation in mouse macrophages, although the biological activity of
thailandolides has not been reported. The structure elucidation