title: Shornephine A: structure, chemical stability, and P-glycoprotein inhibitory properties of a rare diketomorpholine from an Australian marine-derived Aspergillus sp.
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.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland , St. Lucia, QLD 4072, Australia.
authors.forename: Zeinab G
authors.initials: ZG
authors.lastname: Khalil
authors.forename: Xiao-cong
authors.initials: XC
authors.lastname: Huang
authors.forename: Ritesh
authors.initials: R
authors.lastname: Raju
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Piggott
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Capon
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D000818:Animals; D001230:Aspergillus; D001315:Australia; D045744:Cell Line, Tumor; D054659:Diketopiperazines / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D006801:Humans; D008386:Marine Biology; D015394:Molecular Structure; D009025:Morpholines / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D054659:Diketopiperazines; D009025:Morpholines; C000595483:shornephine A