Design and synthesis of a screening library using the natural product scaffold 3-chloro-4-hydroxyphenylacetic acid
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24/04/2015
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Resumo |
The fungal metabolite 3-chloro-4-hydroxyphenylacetic acid (1) was utilized in the generation of a unique drug-like screening library using parallel solution-phase synthesis. A 20-membered amide library (3–22) was generated by first converting 1 to methyl (3-chloro-4-hydroxyphenyl)acetate (2), then reacting this scaffold with a diverse series of primary amines via a solvent-free aminolysis procedure. The structures of the synthetic analogues (3–22) were elucidated by spectroscopic data analysis. The structures of compounds 8, 12, and 22 were confirmed by single X-ray crystallographic analysis. All compounds were evaluated for cytotoxicity against a human prostate cancer cell line (LNCaP) and for antiparasitic activity toward Trypanosoma brucei brucei and Plasmodium falciparum and showed no significant activity at 10 μM. The library was also tested for effects on the lipid content of LNCaP and PC-3 prostate cancer cells, and it was demonstrated that the fluorobenzyl analogues (12–14) significantly reduced cellular phospholipid and neutral lipid levels. |
Formato |
application/pdf |
Identificador | |
Publicador |
ACS Publications |
Relação |
http://eprints.qut.edu.au/83531/13/83531.pdf DOI:10.1021/np500856u Kumar, Rohitesh, Sadowski, Martin C., Levrier, Claire, Nelson, Colleen C., Jones, Amy J., Holleran, John P., Avery, Vicky M., Healy, Peter C., & Davis, Rohan A. (2015) Design and synthesis of a screening library using the natural product scaffold 3-chloro-4-hydroxyphenylacetic acid. Journal of Natural Products, 78(4), pp. 914-918. http://purl.org/au-research/grants/NHMRC/1024314 http://purl.org/au-research/grants/NHMRC/1067728 http://purl.org/au-research/grants/ARC/LE0668477 http://purl.org/au-research/grants/ARC/LE0237908 http://purl.org/au-research/grants/ARC/LP120200339 http://purl.org/au-research/grants/ARC/LP120200557 |
Direitos |
Copyright 2015 The American Chemical Society and American Society of Pharmacognosy |
Fonte |
School of Biomedical Sciences; Faculty of Health; Institute of Health and Biomedical Innovation |
Palavras-Chave | #030502 Natural Products Chemistry #Drug design #natural products #drug discovery #drug synthesis #fungal NP 3-chloro-4-hydrocyphenylacetic acid |
Tipo |
Journal Article |