Semisynthesis and Cytotoxic Evaluation of an Ether Analogue Library Based on a Polyhalogenated Diphenyl Ether Scaffold Isolated from a Lamellodysidea Sponge

The known oxygenated polyhalogenated diphenyl ether, 2-(2',4'-dibromophenoxy)-3,5-dibromophenol ( ), with previously reported activity in multiple cytotoxicity assays was isolated from the sponge sp. and proved to be an amenable scaffold for semisynthetic library generation. The phenol gro...

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Published inMarine drugs Vol. 22; no. 1; p. 33
Main Authors Ramage, Kelsey S, Lock, Aaron, White, Jonathan M, Ekins, Merrick G, Kiefel, Milton J, Avery, Vicky M, Davis, Rohan A
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 01.01.2024
Subjects
Breast cancer
Cancer
Carbon
Cell lines
Chromatography
Crystallography
Cytotoxicity
Dibromophenol
Diphenyl ether
Dysideidae
Enzymes
Halogens
Kinases
Lamellodysidea
Libraries
natural product
Natural products
NMR
Nuclear magnetic resonance
oxygenated polyhalogenated diphenyl ether
Phenols
Prostate
Prostate cancer
Scaffolds
Semisynthesis
Single crystals
Toxicity
Tumor cell lines
X-ray diffraction
X-ray diffraction analysis
United States > US
semisynthesis
prostate cancer
Lamellodysidea
natural product
breast cancer
Dysideidae
oxygenated polyhalogenated diphenyl ether
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Summary:The known oxygenated polyhalogenated diphenyl ether, 2-(2',4'-dibromophenoxy)-3,5-dibromophenol ( ), with previously reported activity in multiple cytotoxicity assays was isolated from the sponge sp. and proved to be an amenable scaffold for semisynthetic library generation. The phenol group of was targeted to generate 12 ether analogues in low-to-excellent yields, and the new library was fully characterized by NMR, UV, and MS analyses. The chemical structures for , , and were additionally determined via single-crystal X-ray diffraction analysis. All natural and semisynthetic compounds were evaluated for their ability to inhibit the growth of DU145, LNCaP, MCF-7, and MDA-MB-231 cancer cell lines. Compound was shown to have near-equivalent activity compared to scaffold in two in vitro assays, and the activity of the compounds with an additional benzyl ring appeared to be reliant on the presence and position of additional halogens.
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ISSN:1660-3397
1660-3397
DOI:10.3390/md22010033