Cinnabaramides A−G:  Analogues of Lactacystin and Salinosporamide from a Terrestrial Streptomycete

• Published in: Journal of natural products (Washington, D.C.) Vol. 70; no. 2; pp. 246 - 252
• Main Authors: Stadler, Marc, Bitzer, Jens, Mayer-Bartschmid, Anke, Müller, Hartwig, Benet-Buchholz, Jordi, Gantner, Florian, Tichy, Hans-Volker, Reinemer, Peter, Bacon, Kevin B
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.02.2007; Amer Chemical Soc; American Society of Pharmacognosy
• Subjects: Acetylcysteine - analogs & derivatives; Acetylcysteine - blood; Acetylcysteine - chemistry; Acetylcysteine - isolation & purification; Acetylcysteine - pharmacology; Antibiotics, microbial producers, chemotherapic agents, antiseptics, disinfecting agents; Applied microbiology; Biological and medical sciences; Chemistry, Medicinal; Chemotherapic agents; Crystallography, X-Ray; Fundamental and applied biological sciences. Psychology; Humans; Lactones - blood; Lactones - isolation & purification; Lactones - pharmacology; Life Sciences & Biomedicine; Microbiology; Molecular Conformation; Molecular Structure; Pharmacology & Pharmacy; Plant Sciences; Proteasome Inhibitors; Pyrroles - blood; Pyrroles - isolation & purification; Pyrroles - pharmacology; Science & Technology; Streptomyces; Streptomyces - chemistry; Streptomycetes; PROTEASOME INHIBITOR; 20S; NPI-0052; Antineoplastic agent; Multicatalytic endopeptidase complex; Lactam; NMR spectrometry; Selectivity; Phylogeny; Pyrrolidine derivatives; Actinomycetales; Marine environment; Production; Bacteria; Human; Terrestrial environment; Streptomycetaceae; Enzyme; Streptomyces; Lactone; In vitro; Biological activity; Peptidases; Microbial origin; Thioester; Hydrolases; Isolation; Actinomycetes; Inhibitor; Structural analysis; Crystalline structure
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np060162u

The cinnabaramides A−G (1−7) were isolated from a terrestrial strain of Streptomyces as potent and selective inhibitors of the human 20S proteasome. Their chemical and biological properties resemble those of salinosporamide A, a recently identified lead compound from an obligate marine actinomycete, which is currently under development as an anticancer agent. Cinnabaramides F and G (6, 7) combine essential structural features of salinosporamide A and lactacystin and show about equal potency in vitro, with IC50 values in the 1 nM range. The properties and phylogenetic position of the producer organism, the production and isolation of compounds 1−7, their structure elucidation by MS and NMR, and their biological activities are reported. Additionally, an X-ray crystal structure was obtained from cinnabaramide A (1).