- Title
- Synthesis and anticancer activity of focused compound libraries from the natural product lead, oroidin
- Creator
- Dyson, Lauren; Wright, Anthony D.; Young, Kelly A.; Sakoff, Jennette A.; McCluskey, Adam
- Relation
- Bioorganic and Medicinal Chemistry Vol. 22, Issue 5, p. 1690-1699
- Publisher Link
- http://dx.doi.org/10.1016/j.bmc.2014.01.021
- Publisher
- Pergamon Press
- Resource Type
- journal article
- Date
- 2014
- Description
- Oroidin (1), (E)-N-(3-(2-amino-1H-imidazol-4-yl)allyl)-4,5-dibromo-1H-pyrrole-2-carboxamide, is a pyrrole alkaloid isolated from the marine sponge Agelas oroides. Routine screening in a panel of twelve cancer cell lines revealed 1 to be poorly cytotoxic with the 50% growth inhibition concentration (GI50) of 42 μM in MCF-7 (breast) cells and 24 μM in A2780 (ovarian) cells and >50 μM in all other cell lines tested. The development of eight focused libraries comprising thirty compounds total identified N-(biphenyl-4-ylmethyl)-1H-pyrrole-2-carboxamide (4l), N-benzyl-4,5-dibromo-1H-pyrrole-2-carboxamide (5a) and N-(biphenyl-4-ylmethyl)-4,5-dibromo-1H-pyrrole-2-carboxamide (5l) as potent inhibitors of cell growth in our panel of cell lines. Of these compounds GI50 values of <5 μM were observed with 4l against HT29 (colon) and SW480 (colon); 5a against HT29; and 5l against HT29, SW480, MCF-7, A431 (skin), Du145 (prostate), BE2-C (neuroblastoma) and MIA (pancreas) cell lines. As a cancer class, colon cancer appears to be more sensitive to the oroidin series of compounds, with analogue 5l being the most active.
- Subject
- oroidin; focused libraries; cytotoxic compound; natural product leads; sponges; synthesis
- Identifier
- http://hdl.handle.net/1959.13/1294406
- Identifier
- uon:18787
- Identifier
- ISSN:0968-0896
- Language
- eng
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