Chrysosporazines A–E: P‑Glycoprotein Inhibitory Piperazines from an Australian Marine Fish Gastrointestinal Tract-Derived Fungus, Chrysosporium sp. CMB-F214

Chemical analysis of Chrysosporium sp. CMB-F214, yielded five new piperazines, chrysosporazines A–E (1–5), with structures assigned by spectroscopic and X-ray analyses and biosynthetic considerations. The chrysosporazines 2–5 exist as an equilibrium of major and minor N-acyl rotamers, while 1–3 inco...

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Bibliographic Details
Published in:Organic letters 2019-10, Vol.21 (19), p.8097-8100
Main Authors: Elbanna, Ahmed H, Khalil, Zeinab G, Bernhardt, Paul V, Capon, Robert J
Format: Article
Language:English
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Summary:Chemical analysis of Chrysosporium sp. CMB-F214, yielded five new piperazines, chrysosporazines A–E (1–5), with structures assigned by spectroscopic and X-ray analyses and biosynthetic considerations. The chrysosporazines 2–5 exist as an equilibrium of major and minor N-acyl rotamers, while 1–3 incorporate an unprecedented hexahydro-6H-pyrazino­[1,2-b]­isoquinolin-6-one scaffold. The noncytotoxic chrysosporazines reverse doxorubicin drug resistance in P-glycoprotein overexpressing colon carcinoma cells (SW620 Ad300), with 2 delivering a comparable gain in sensitivity to the positive control, verapamil.
ISSN:1523-7060
1523-7052
DOI:10.1021/acs.orglett.9b03094