Design and synthesis of a screening library using the natural product scaffold 3-chloro-4-hydroxyphenylacetic acid

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.

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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.

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1 citations in Scopus
1 citations in Web of Science®
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ID Code: 83531
Item Type: Journal Article
Refereed: Yes
Additional Information: Publication Date (Web): March 24, 2015
Additional URLs:
Keywords: Drug design, natural products, drug discovery, drug synthesis, fungal NP 3-chloro-4-hydrocyphenylacetic acid
DOI: 10.1021/np500856u
ISSN: 1520-6025
Subjects: Australian and New Zealand Standard Research Classification > CHEMICAL SCIENCE (030000) > ORGANIC CHEMISTRY (030500) > Natural Products Chemistry (030502)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2015 The American Chemical Society and American Society of Pharmacognosy
Deposited On: 13 Apr 2015 23:01
Last Modified: 01 May 2016 18:06

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