Design and Synthesis of a Screening Library Using the Natural Product Scaffold 3-Chloro-4-hydroxyphenylacetic Acid
| Autor: | Martin C. Sadowski, Colleen C. Nelson, Amy J. Jones, John P. Holleran, Rohitesh Kumar, Rohan A. Davis, Vicky M. Avery, Claire Levrier, Peter Conrad Healy |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
Antiparasitic medicine.drug_class Stereochemistry Plasmodium falciparum Trypanosoma brucei brucei Molecular Conformation Pharmaceutical Science Trypanosoma brucei Crystallography X-Ray Analytical Chemistry Antimalarials Structure-Activity Relationship chemistry.chemical_compound Aminolysis Amide Drug Discovery LNCaP medicine Combinatorial Chemistry Techniques Humans Cytotoxicity Nuclear Magnetic Resonance Biomolecular Phenylacetates Pharmacology Biological Products Natural product Molecular Structure biology Organic Chemistry biology.organism_classification Combinatorial chemistry 4-Hydroxyphenylacetic acid Complementary and alternative medicine chemistry Molecular Medicine |
| Zdroj: | Journal of Natural Products. 78:914-918 |
| ISSN: | 1520-6025 0163-3864 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|