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1. Chem Asian J. 2012 Mar 30. doi: 10.1002/asia.201101049. [Epub ahead of print]

Lamellarins as Inhibitors of P-Glycoprotein-Mediated Multidrug Resistance in a
Human Colon Cancer Cell Line.

Plisson F, Huang XC, Zhang H, Khalil Z, Capon RJ.

Division of Chemistry and Structural Biology, Institute for Molecular Bioscience,
The University of Queensland, 360 Carmody Road, St Lucia, Brisbane, 4072,
Queensland (Australia), Fax: (+61) 7-334-62090.

Chemical analysis of a Didemnum sp. (CMB-01656) collected during scientific Scuba
operations off Wasp Island, New South Wales, yielded five new lamellarins A1 (1),
A2 (2), A3 (3), A4 (4) and A5 (5) and eight known lamellarins C (6), E (7), K
(8), M (9), S (10), T (11), X (12) and χ (13). Analysis of a second Didemnum sp.
(CMB-02127) collected during scientific trawling operations along the Northern
Rottnest Shelf, Western Australia, yielded the new lamellarin A6 (14) and two
known lamellarins G (15) and Z (16). Structures were assigned to 1-16 on the
basis of detailed spectroscopic analysis with comparison to literature data and
authentic samples. Access to this unique library of natural lamellarins (1-16)
provided a rare opportunity for structure-activity relationship (SAR)
investigations, probing interactions between lamellarins and the ABC transporter
efflux pump P-glycoprotein (P-gp) with a view to reversing multidrug resistance
in a human colon cancer cell line (SW620 Ad300). These SAR studies, which were
expanded to include the permethylated lamellarin derivative (17) and a series of
lamellarin-inspired synthetic coumarins (19-24) and isoquinolines (25-26),
successfully revealed 17 as a promising new non-cytotoxic P-gp inhibitor
pharmacophore.

Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PMID: 22473938 [PubMed - as supplied by publisher]