Salinosporamide

The salinosporamides are a group of closely related chemical compounds isolated from marine bacteria in the genus Salinispora.^[1]^[2]^[3]^[4] They possess a densely functionalized γ-lactam-β-lactone bicyclic core.

Salinosporamide A has attracted interest for its potential use in treating various types of cancer.^[5]^[6]^[7]^[8]

In addition, a variety of synthetic analogs have been prepared.^[9]

Chemical structures

Salinosporamide A
Salinosporamide B
Salinosporamide C
Salinosporamide D
Salinosporamide E
Salinosporamide F
Salinosporamide G
Salinosporamide H
Salinosporamide I
Salinosporamide J
Salinosporamide K

References

^ Feling, Robert H.; Buchanan, Greg O.; Mincer, Tracy J.; Kauffman, Christopher A.; Jensen, Paul R.; Fenical, William (2003). "Salinosporamide A: A Highly Cytotoxic Proteasome Inhibitor from a Novel Microbial Source, a Marine Bacterium of the New Genus Salinospora". Angewandte Chemie International Edition. 42 (3): 355–7. doi:10.1002/anie.200390115. PMID 12548698.
^ Philip G. Williams; Greg O. Buchanan; Robert H. Feling; Christopher A. Kauffman; Paul R. Jensen & William Fenical (2005). "New Cytotoxic Salinosporamides from the Marine Actinomycete Salinispora tropica". J. Org. Chem. 70 (16): 6196–6203. doi:10.1021/jo050511+. PMID 16050677.
^ Reed, Katherine A.; Manam, Rama Rao; Mitchell, Scott S.; Xu, Jianlin; Teisan, Sy; Chao, Ta-Hsiang; Deyanat-Yazdi, Gordafaried; Neuteboom, Saskia T. C.; et al. (2007). "Salinosporamides D−J from the Marine ActinomyceteSalinispora tropica, Bromosalinosporamide, and Thioester Derivatives Are Potent Inhibitors of the 20S Proteasome". Journal of Natural Products. 70 (2): 269–76. doi:10.1021/np0603471. PMID 17243724.
^ Eustáquio, Alessandra S.; Nam, Sang-Jip; Penn, Kevin; Lechner, Anna; Wilson, Micheal C.; Fenical, William; Jensen, Paul R.; Moore, Bradley S. (2011). "The Discovery of Salinosporamide K from the Marine Bacterium "Salinispora pacifica" by Genome Mining Gives Insight into Pathway Evolution". ChemBioChem. 12 (1): 61–4. doi:10.1002/cbic.201000564. PMC 3088357. PMID 21154492.
^ Fenical, William; Jensen, Paul R.; Palladino, Michael A.; Lam, Kin S.; Lloyd, G. Kenneth; Potts, Barbara C. (2009). "Discovery and development of the anticancer agent salinosporamide A (NPI-0052)". Bioorganic & Medicinal Chemistry. 17 (6): 2175–80. doi:10.1016/j.bmc.2008.10.075. PMC 2814440. PMID 19022674.
^ Lam, Kin S.; Lloyd, G. Kenneth; Neuteboom, Saskia T. C.; Palladino, Michael A.; Sethna, Kobi M.; Spear, Matthew A.; Potts, Barbara C. (2009). "Chapter 12. From Natural Product to Clinical Trials: NPI-0052 (Salinosporamide A), a Marine Actinomycete-Derived Anticancer Agent". Natural Product Chemistry for Drug Discovery. p. 355. doi:10.1039/9781847559890-00355. ISBN 978-0-85404-193-0.
^ Gulder, Tobias A. M.; Moore, Bradley S. (2010). "Salinosporamide Natural Products: Potent 20 S Proteasome Inhibitors as Promising Cancer Chemotherapeutics". Angewandte Chemie International Edition. 49 (49): 9346–67. doi:10.1002/anie.201000728. PMC 3103133. PMID 20927786.
^ WO 2006118973, Palladino, Michael; Potts, Barbara Christine & Macherla, Venkata Rami Reddy et al., "Methods of using heterobyclic compounds for treatment of rectal cancer", published 2006-11-09, assigned to Nereus Pharmaceuticals Inc.
^ Nett, Markus; Gulder, Tobias A. M.; Kale, Andrew J.; Hughes, Chambers C.; Moore, Bradley S. (2009). "Function-Oriented Biosynthesis of β-Lactone Proteasome Inhibitors inSalinispora tropica". Journal of Medicinal Chemistry. 52 (19): 6163–7. doi:10.1021/jm901098m. PMC 2771571. PMID 19746976.

External links

Media related to Salinosporamides at Wikimedia Commons

[1] Feling, Robert H.; Buchanan, Greg O.; Mincer, Tracy J.; Kauffman, Christopher A.; Jensen, Paul R.; Fenical, William (2003). "Salinosporamide A: A Highly Cytotoxic Proteasome Inhibitor from a Novel Microbial Source, a Marine Bacterium of the New Genus Salinospora". Angewandte Chemie International Edition. 42 (3): 355–7. doi:10.1002/anie.200390115. PMID 12548698.

[2] Philip G. Williams; Greg O. Buchanan; Robert H. Feling; Christopher A. Kauffman; Paul R. Jensen & William Fenical (2005). "New Cytotoxic Salinosporamides from the Marine Actinomycete Salinispora tropica". J. Org. Chem. 70 (16): 6196–6203. doi:10.1021/jo050511+. PMID 16050677.

[3] Reed, Katherine A.; Manam, Rama Rao; Mitchell, Scott S.; Xu, Jianlin; Teisan, Sy; Chao, Ta-Hsiang; Deyanat-Yazdi, Gordafaried; Neuteboom, Saskia T. C.; et al. (2007). "Salinosporamides D−J from the Marine ActinomyceteSalinispora tropica, Bromosalinosporamide, and Thioester Derivatives Are Potent Inhibitors of the 20S Proteasome". Journal of Natural Products. 70 (2): 269–76. doi:10.1021/np0603471. PMID 17243724.

[4] Eustáquio, Alessandra S.; Nam, Sang-Jip; Penn, Kevin; Lechner, Anna; Wilson, Micheal C.; Fenical, William; Jensen, Paul R.; Moore, Bradley S. (2011). "The Discovery of Salinosporamide K from the Marine Bacterium "Salinispora pacifica" by Genome Mining Gives Insight into Pathway Evolution". ChemBioChem. 12 (1): 61–4. doi:10.1002/cbic.201000564. PMC 3088357. PMID 21154492.

[5] Fenical, William; Jensen, Paul R.; Palladino, Michael A.; Lam, Kin S.; Lloyd, G. Kenneth; Potts, Barbara C. (2009). "Discovery and development of the anticancer agent salinosporamide A (NPI-0052)". Bioorganic & Medicinal Chemistry. 17 (6): 2175–80. doi:10.1016/j.bmc.2008.10.075. PMC 2814440. PMID 19022674.

[6] Lam, Kin S.; Lloyd, G. Kenneth; Neuteboom, Saskia T. C.; Palladino, Michael A.; Sethna, Kobi M.; Spear, Matthew A.; Potts, Barbara C. (2009). "Chapter 12. From Natural Product to Clinical Trials: NPI-0052 (Salinosporamide A), a Marine Actinomycete-Derived Anticancer Agent". Natural Product Chemistry for Drug Discovery. p. 355. doi:10.1039/9781847559890-00355. ISBN 978-0-85404-193-0.

[7] Gulder, Tobias A. M.; Moore, Bradley S. (2010). "Salinosporamide Natural Products: Potent 20 S Proteasome Inhibitors as Promising Cancer Chemotherapeutics". Angewandte Chemie International Edition. 49 (49): 9346–67. doi:10.1002/anie.201000728. PMC 3103133. PMID 20927786.

[8] WO 2006118973, Palladino, Michael; Potts, Barbara Christine & Macherla, Venkata Rami Reddy et al., "Methods of using heterobyclic compounds for treatment of rectal cancer", published 2006-11-09, assigned to Nereus Pharmaceuticals Inc.

[9] Nett, Markus; Gulder, Tobias A. M.; Kale, Andrew J.; Hughes, Chambers C.; Moore, Bradley S. (2009). "Function-Oriented Biosynthesis of β-Lactone Proteasome Inhibitors inSalinispora tropica". Journal of Medicinal Chemistry. 52 (19): 6163–7. doi:10.1021/jm901098m. PMC 2771571. PMID 19746976.

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