Shornephine A: structure, chemical stability, and P-Glycoprotein inhibitory properties of a rare Diketomorpholine from an Australian marine-derived Aspergillus sp.

Khalil, Zeinab G., Huang, Xiao-cong, Raju, Ritesh, Piggott, Andrew M. and Capon, Robert J. (2014) Shornephine A: structure, chemical stability, and P-Glycoprotein inhibitory properties of a rare Diketomorpholine from an Australian marine-derived Aspergillus sp.. Journal of Organic Chemistry, 79 18: 8700-8705. doi:10.1021/jo501501z


Author Khalil, Zeinab G.
Huang, Xiao-cong
Raju, Ritesh
Piggott, Andrew M.
Capon, Robert J.
Title Shornephine A: structure, chemical stability, and P-Glycoprotein inhibitory properties of a rare Diketomorpholine from an Australian marine-derived Aspergillus sp.
Formatted title
Shornephine A: structure, chemical stability, and P-Glycoprotein inhibitory properties of a rare Diketomorpholine from an Australian marine-derived Aspergillus sp.
Journal name Journal of Organic Chemistry   Check publisher's open access policy
ISSN 0022-3263
1520-6904
Publication date 2014-09-19
Year available 2014
Sub-type Article (original research)
DOI 10.1021/jo501501z
Open Access Status Not yet assessed
Volume 79
Issue 18
Start page 8700
End page 8705
Total pages 6
Place of publication Washington, DC, United States
Publisher American Chemical Society
Language eng
Subject 1605 Organic Chemistry
2700 Medicine
Abstract Chemical analysis of an Australian marine sediment-derived Aspergillus sp. (CMB-M081F) yielded the new diketomorpholine (DKM) shomephine A (1) together with two known and one new diketopiperazine (DKP), 15b-beta-hydroxy-5-N-acetyladreemin (2), 5-N-acetyladreemin (3), and 15b-beta-methoxy-5-N-acetyladreemin (4), respectively. Structure elucidation of 1-4 was achieved by detailed spectroscopic analysis, supported by chemical degradation and derivatization, and biosynthetic considerations. The DKM (1) underwent a facile (auto) acid-mediated methanolysis to yield seco-shornephine A methyl ester (1a). Our mechanistic explanation of this transformation prompted us to demonstrate that the acid-labile and solvolytically unstable DKM scaffold can be stabilized by N-alkylation. Furthermore, we demonstrate that at 20 mu M shornephine A (1) is a noncytotoxic inhibitor of P-glycoprotein-mediated drug efflux in multidrug-resistant human colon cancer cells.
Formatted abstract
Chemical analysis of an Australian marine sediment-derived Aspergillus sp. (CMB-M081F) yielded the new diketomorpholine (DKM) shornephine A (1) together with two known and one new diketopiperazine (DKP), 15b-β-hydroxy-5-N-acetyladreemin (2), 5-N-acetyladreemin (3), and 15b-β-methoxy-5-N-acetyladreemin (4), respectively. Structure elucidation of 1–4 was achieved by detailed spectroscopic analysis, supported by chemical degradation and derivatization, and biosynthetic considerations. The DKM (1) underwent a facile (auto) acid-mediated methanolysis to yield seco-shornephine A methyl ester (1a). Our mechanistic explanation of this transformation prompted us to demonstrate that the acid-labile and solvolytically unstable DKM scaffold can be stabilized by N-alkylation. Furthermore, we demonstrate that at 20 μM shornephine A (1) is a noncytotoxic inhibitor of P-glycoprotein-mediated drug efflux in multidrug-resistant human colon cancer cells.
Keyword Multiple drug resistance
6-Hydroxydeoxybrevianamide E
Heterocyclic compound
Indole alkaloids
Tumor cells
Biosynthesis
Derivatives
5-N-Acetylardeemin
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID LP120100088
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
 
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