Activity of 6-aryl-pyrrolo[2,3-d]pyrimidine-4-amines to Tetrahymena
Journal article, Peer reviewed
N o t i c e: this is the author’s version of a work that was accepted for publication in bioorganic chemistry. changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. changes may have been made to this work since it was submitted for publication. a definitive version was subsequently published in bioorganic chemistry, http://dx.doi.org/10.1016/j.bioorg.2012.06.003
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2012-06-05Metadata
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Kaspersen, S.J., Sundby, E., Charnock, C. & Hoff, B.H. (2012). Activity of 6-aryl-pyrrolo[2,3-d]pyrimidine-4-amines to Tetrahymena. Bioorganic chemistry, In Press. http://dx.doi.org/10.1016/j.bioorg.2012.06.003Abstract
A series 6-aryl-pyrrolo[2,3-d]pyrimidine-4-amines (43 compounds), some of which are epidermal growth 22 factor tyrosine kinase inhibitors, were tested for their protozoal toxicity using an environmental Tetrahy- 23 mena strain as model organism. The protozoacidal activity of the analogues was found to be highly 24 dependent on a 4-hydroxyl group at the 6-aryl ring, and a chiral 1-phenylethanamine substituent in posi- 25 tion 4. Further, the potency was affected by the aromatic substitution pattern of the phenylethanamine: 26 the unsubstituted, the meta-fluoro and the para-bromo substituted derivatives had the lowest minimum 27 protozoacidal concentrations (8–16 lg/mL). Surprisingly, both enantiomers were found to have high 28 potency suggesting that this compound class could have several modes of action. No correlation was 29 found between the compounds protozoacidal activity and the in vitro epidermal growth factor receptor 30 tyrosine kinase inhibitory potency. This suggests that the observed antimicrobial effects are related to 31 other targets. Testing towards a panel of kinases indicated several alternative modes of action