Design and Application of a High-Throughput, High-Content Screening System for Natural Product Inhibitors of the Human Parasite Trichomonas vaginalis.
ACS Infect Dis
; 5(8): 1456-1470, 2019 08 09.
Article
in En
| MEDLINE
| ID: mdl-31265248
ABSTRACT
It is estimated that Trichomonas vaginalis affects an astonishing 3.9% of the world's population, and while many of those infected are asymptomatic, progression of the disease can lead to serious health problems. Currently, the nitroimidazoles constitute the only drug class approved to treat trichomoniasis in the United States, which makes the spread of drug resistance a realistic concern. We developed a new image-based, high-throughput, and high-content assay for testing natural products (purified compounds and extracts) for antitrichomonal activity. Applying this assay system to a library of fungal natural product extracts led to the identification of three general classes of natural product inhibitors that exhibited moderate to strong activities against T. vaginalis anthraquinones, xanthone-anthraquinone heterodimers, and decalin-linked tetramic-acid-containing metabolites. The tetramate natural products emerged as the most promising candidate molecules with pyrrolocin A (51) exhibiting potent activity against the parasite (EC50 = 60 nM), yet this metabolite showed limited toxicity to mammalian cell lines (selectivity index values of 100 and 167 versus 3T3 fibroblast and Ect1 normal cervical cells, respectively). The imaging-based assay system is a powerful tool for the bioassay-guided purification of single-component antitrichomonal biomolecules from complex natural product mixtures.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Trichomonas vaginalis
/
Biological Products
/
Image Processing, Computer-Assisted
/
Drug Discovery
/
High-Throughput Screening Assays
/
Antiprotozoal Agents
Type of study:
Diagnostic_studies
/
Screening_studies
Limits:
Female
/
Humans
Language:
En
Journal:
ACS Infect Dis
Year:
2019
Document type:
Article
Affiliation country:
United States