Dihydrocompactin,a new potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme-A reductase from Penicillium citrinum.

Abstract

Compactin (Fig. Later, ENDO et al.2> reported their isolation of compactin (designated as ML-236B) together with ML-236A and ML-236C as hypocholesteremic agents from Penicillium citrinum. ENDO also reported monacolin K from Monascus ruber3). Independently, the same compound (named mevinolin) was isolated by ALBERTS et al.1) from Aspergillus terreus. 4a, 5-Dihydromevinolin (Fig. All of these five structurally-related entities are potent competitive inhibitors of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase (EC 1.1.1.34)2-1), the rate-limiting enzyme in cholesterol synthesis, with mevinolin being the most potent. However, compactin is the most extensively studied. Its hypocholesteremic acitivity in several animal species including human subjects has been demonstrated8~12) and a review of its pharmacology was also publi-shed13).