Isochromophilones

Isochromophilones VII (190) and VIII (191) from a Penicillium sp. inhibit diacylglycerol acytransferase activity with IC5o values of 20.0 and 127 pM and acyl-CoA cholesterol acyltransferase activity with IC50 values of 24.5 and 47.0, respectively. They also show moderate antimicrobial activity [153]. 

Matsuzaki K, Ikeda H, Masuma R, Tanaka H, Omura S (1995) Isochromophilones I and II, Novel Inhibitors against gpl20-CD4 Binding Produced by Penicillium multicolor FO-2338 I. Screening, Taxonomy, Ferrmentation, Isolation and Biological Activity. J Antibiot 48 703... 

Arai N, Shiomi K, Tomoda H, Tabata N, Yang DJ, Masuma R, Kawakubo T, Omura S (1995) Isochromophilones III VI, Inhibitors of Acyl-CoA Cholesterol Acyltransferase Produced by Penicillium multicolor FO-3216. J Antibiot 48 696... 

Michael AP, Grace EJ, Kotiw M, Barrow RA (2003) Isochromophilone IX, a Novel GABA-Containing Metabolite Isolated from a Cultured Fungus, Penicillium sp. Aust J Chem 56 13... 

Isochromophilones I (14, 15), the new gp 120-CD4 binding inhibitors, were isolated from a culture broth of Penicillium multicolor FO-2338 grown on a medium with carbon and nitrogen sources. Their amounts in the medium were 2 mg/1 and their chemical structures were elucidated... 

Isochromophilones I (14 and 15) inhibited gpl20-CD4 binding with IC50 values of 6.6 and 3.9 pM, respectively, by ELISA method. Isochromophilone (15) exhibited anti-HIV activity at 25 pM, but did not affect cell proliferation in lymphocytes at the same concentration although it inhibited somewhat the cell proliferation at 250 pM. 

Isochromophilones II (16 and 17) were inactive against bacteria (Bacillus subtilis, Micrococcus luteus, Escherichia coli and Staphylococcus aureus) and fungi (Candida albicans, Aspergillus niger and Piricularia oryzae) at 1.0 mg/ml on paper disc method. 

New azaphilones named isochromophilones III-VI (18-21) were isolated from the culture broth of Penicillium multicolor FO-3216 as inhibitors of ACAT. Their structures were elucidated by NMR and other spectroscopic analyses. The IC50 values of isochromophilones (17-20) (ACAT) activity in an enzyme assay using rat liver microsomes were calculated to be 110, 50, 50 and 120 pM, respectively [79]. 

Isochromophilone IX (24), a novel GABA-containing metabolite, was isolated from a cultured fungus, Penicillium sp. [81]. 

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