Synthesis and anticancer activity of focused compound libraries from the natural product lead, oroidin.

Abstract

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.

• Authors: Lauren Dyson, Anthony D Wright, Kelly A Young, Jennette A Sakoff, Adam McCluskey
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 22 Issue 5 Pg. 1690-9 (Mar 01 2014) ISSN: 1464-3391 [Electronic] England
• PMID: 24508308 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Biological Products
• Pyrroles
• oroidin

Topics

• Animals
• Biological Products
• Cell Proliferation
• Molecular Structure
• Pyrroles (chemical synthesis, chemistry)
• Structure-Activity Relationship