Repurposing sodium stibogluconate as an uracil DNA glycosylase inhibitor against prostate cancer using a time-resolved oligonucleotide-based drug screening platform.
Bioorg Chem
; 144: 107176, 2024 Mar.
Article
in En
| MEDLINE
| ID: mdl-38330721
ABSTRACT
Repurposing drugs can significantly reduce the time and costs associated with drug discovery and development. However, many drug compounds possess intrinsic fluorescence, resulting in aberrations such as auto-fluorescence, scattering and quenching, in fluorescent high-throughput screening assays. To overcome these drawbacks, time-resolved technologies have received increasing attention. In this study, we have developed a rapid and efficient screening platform based on time-resolved emission spectroscopy in order to screen for inhibitors of the DNA repair enzyme, uracil-DNA glycosylase (UDG). From a database of 1456 FDA/EMA-approved drugs, sodium stibogluconate was discovered as a potent UDG inhibitor. This compound showed synergistic cytotoxicity against 5-fluorouracil-resistant cancer cells. This work provides a promising future for time-resolved technologies for high-throughput screening (HTS), allowing for the swift identification of bioactive compounds from previously overlooked scaffolds due to their inherent fluorescence properties.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prostatic Neoplasms
/
Uracil-DNA Glycosidase
Type of study:
Diagnostic_studies
/
Screening_studies
Limits:
Humans
/
Male
Language:
En
Journal:
Bioorg Chem
Year:
2024
Type:
Article
Affiliation country:
China