Purpactin C

Penicillium purpurogenum FO-608, a soil isolate, was found to produce a series of new inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). Three active compounds, designated purpactins, A, B and C, were isolated from the fermentation broth of the producing strain by solvent extraction, silica gel column chromatography and HPLC. Purpactins inhibit ACAT activity in an enzyme assay system using rat liver microsomes with IC50 values of 121 approximately 126 microM. Purpactin A also inhibited cholesterol ester formation in J 774 macrophages, indicating the inhibition of ACAT activity in the living cells by purpactin A.

The structure of purpactins, novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors, was determined by spectroscopic analyses. Purpactin A was deduced to be 3-1'-acetoxy-11-hydroxy-4-methoxy-9-methyl-3'-methylbutyl-5H, 7H-dibenzo[b,g]-1,5-dioxocin-5-one, purpactin B was 5-1''-acetoxy-6'-hydroxymethyl-4-methoxy-4'-methyl-3''-methylbutyl-spiro [benzofuran-2,1'-cyclohexa-3',5'-diene]-2',3(2H)-dione and purpactin C was 5-1''-acetoxy-6'-formyl-4-methoxy-4'-methyl-3''-methylbutyl-spiro [benzofuran-2,1'-cyclohexa-3',5'-diene]-2',3(2H)-dione. Purpactin A was attributed to 1'-O-acetylpenicillide.

Talaromyces purpureogenus CFRM02 pigments are non-toxic to Artemia franciscana. Further, in acute toxicity study, single dose (50, 300, 1000 and 2000 mg/kg body weight) pigment was administered to female Wistar rats. After 14 days, no evidence of adverse effect on body weight, mortality and clinical signs were observed. Similarly, 28 days sub-acute studies (250-1000 mg/kg body weight) showed no significant changes in food intake, body weight gain and relative weight of vital organs. No signs of toxicity on biochemical, hematological parameters. Histopathological examination of the liver and kidney were normal. There were no marked changes in any of the serum enzymes activities. There were no significant changes in treated and control group (acute and sub-acute). The HRMS data revealed the identification of purpuride, PP-O, PP-R, pentalsamonin, puractin-A, arginine-monascorubrin, purpurquinone-A, ankaflavin, purpactin-C. These results confirmed safety efficacy of T. purpureogenus CFRM02 pigment and suggested applications in food and nutraceuticals.