Design and Synthesis of a Screening Library Using the Natural Product Scaffold 3-Chloro-4-hydroxyphenylacetic Acid.
J Nat Prod
; 78(4): 914-8, 2015 Apr 24.
Article
de En
| MEDLINE
| ID: mdl-25803573
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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Phénylacétates
/
Produits biologiques
Type d'étude:
Diagnostic_studies
/
Screening_studies
Limites:
Humans
/
Male
Langue:
En
Journal:
J Nat Prod
Année:
2015
Type de document:
Article
Pays d'affiliation:
Australie