Amino alcohol acrylonitriles as broad spectrum and tumour selective cytotoxic agents
- Jennifer R. Bakera
- Cecilia C. Russella
- Jayne Gilbertb
- Adam McCluskeya
- Jennette A. Sakoffb
- aChemistry, School of Environmental & Life Sciences, The University of Newcastle, University Drive, Callaghan, NSW 2308, Australia
- bExperimental Therapeutics Group, Department of Medical Oncology, Calvary Mater Newcastle Hospital, Edith Street, Waratah, NSW 2298, Australia
Read the publication that featured this abstractWe have identified specific dichlorophenylacrylonitriles as lead compounds in the development of novel anticancer compounds, notably, (Z)-N-(4-(2-cyano-2-(3,4-dichlorophenyl)vinyl)phenyl)acetamide (1) and ANI-7 (2). Herein we specifically probe the SAR associated with the terminal aromatic ring and associated cytoxicity in a broad range of human cancer cell lines. Synthesis of three focused libraries revealed a poor tolerance for electron withdrawing and donating moieties (Library A). A clear preference for hydrophobic substituents on a terminal piperazine moiety (Library B) with good levels of broad spectrum cytotoxicity, e.g.13a (GI50 2.5–6.0 μM), as did the introduction of a methylene spacer with 13i (4-CH3PhCH2; GI50 1.5–4.5 μM). Removal of the aromatic moiety and installation of simple hydrophobic groups (Library C), in particular an adamantyl moiety, afforded highly active broad spectrum cytotoxic agents with GI50 values ranging from 1.7 μM (14k; 1-adamantyl) to 5.6 μM (14i; pyrrolidine). Within these libraries we note lung cancer selectivity, relative to normal cells, of 13h (fluoro substituted acrylonitrile, GI50 1.6 μM, 9.3-fold selective); the colorectal selectivity of 14h (methylpiperidine analogue, GI50 0.36 μM, 6.9-fold selective) and the breast cancer selectivity of 13f (nitrile substituted acrylonitrile, GI50 2.3–6.0 μM, up to 20-fold selective). The latter was confirmed as a novel AhR ligand and a CYP1A1 activating compound, that likely induces cell death following bioactivation; a phenomenon previously described in breast cancer cell populations.
Get in touch
For more information on flow chemistry systems and services please use the contact methods below.
Call us on +44 (0)1284 728659 or Email us
Resource Centre
R-Series

The Vapourtec R-Series is, quite simply, unrivalled for flow chemistry
- Flexible |
- Precise |
- Automatable
The R-Series is undoubtedly the most versatile, modular flow chemistry system available today.
E-Series

The Vapourtec E-Series is the perfect introductory system for flow chemistry
- Robust |
- Easy to use |
- Affordable
The E-Series is a robust and affordable, entry level flow chemistry system designed for reliability and ease of use.