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.
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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|Item Type:||Journal Article|
|Additional Information:||Publication Date (Web): March 24, 2015|
|Keywords:||Drug design, natural products, drug discovery, drug synthesis, fungal NP 3-chloro-4-hydrocyphenylacetic acid|
|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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