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.

View at publisher

Abstract

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.

Impact and interest:

1 citations in Scopus
Search Google Scholar™
1 citations in Web of Science®

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

Full-text downloads:

9 since deposited on 13 Apr 2015
7 in the past twelve months

Full-text downloads displays the total number of times this work’s files (e.g., a PDF) have been downloaded from QUT ePrints as well as the number of downloads in the previous 365 days. The count includes downloads for all files if a work has more than one.

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
Funding:
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

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page