- Title
- Discovery of acrylonitrile-based small molecules active against Haemonchus contortus
- Creator
- Gordon, Christopher P.; Hizartzidis, Lacey; Tarleton, Mark; Sakoff, Jennette A.; Gilbert, Jayne; Campbell, Bronwyn E.; Gasser, Robin B.; McCluskey, Adam
- Relation
- ARC
- Relation
- MedChemComm Vol. 5, Issue 2, p. 159-164
- Publisher Link
- http://dx.doi.org/10.1039/c3md00255a
- Publisher
- Royal Society of Chemistry
- Resource Type
- journal article
- Date
- 2014
- Description
- We report the discovery of a series of acrylonitrile-containing molecules and α-amino amides which cause 99–100% lethality in H. contortus. Of the 22 acrylonitrile analogues investigated, the most active were 2-cyano-3-[1-(3-dimethylaminopropyl)-2-methyl-1H-indol-3-yl]-N-hexylacrylamide (13a), 2-cyano-3-[1(2-dimethylaminoethyl)-2-methyl-1H-indol-3-yl]-N-hexylacrylamide (13b), 2-cyano-3-{4-[3-(dimethylamino)propoxy]phenyl}-N-octylacrylamide (21), and 2-cyano-3-{1-[3-(dimethylamino)propyl]-1H-pyrrol-2-yl}-N-octylacrylamide (22) with each displaying LD₅₀ values <15 μM whilst the α-amino amide methyl-2-[2-(2-benzoylphenylamino)-2-(4-methoxyphenyl)acetamido]acetate (12a) had an LD₅₀ value of 10 μM. A cytotoxicity screen of the acrylonitrile analogues (13a, 13b, 21 and 22) against nine cancer cell lines indicated modest to high cytotoxicity. In contrast, the α-amino amide 12a displayed very low cytotoxicity, with a maximum of ∼30% cell death at 25 μM (A2780, an ovarian carcinoma derived cell line) and with a mean of 11% cell death across all cell lines evaluated. Thus, 12a is considered a promising lead candidate for the development of a new anthelmintic.
- Subject
- acrylonitrile-containing molecules; α-amino amides; Haemonchus contortus
- Identifier
- http://hdl.handle.net/1959.13/1305084
- Identifier
- uon:20974
- Identifier
- ISSN:2040-2503
- Language
- eng
- Reviewed
- Hits: 2857
- Visitors: 3180
- Downloads: 0
| Thumbnail | File | Description | Size | Format |
|---|