RESUMO
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.
Assuntos
Neoplasias da Próstata , Uracila-DNA Glicosidase , Humanos , Masculino , Uracila-DNA Glicosidase/química , Oligonucleotídeos , Gluconato de Antimônio e Sódio , Avaliação Pré-Clínica de Medicamentos , Reposicionamento de Medicamentos , Detecção Precoce de CâncerRESUMO
EthR is a transcriptional repressor that increases Mycobacterium tuberculosis resistance to ethionamide. In this study, the EthR-DNA interaction has been investigated by native electrospray-ionization mass spectrometry for the first time. The results show that up to six subunits of EthR are able to bind to its operator.
Assuntos
DNA Bacteriano/metabolismo , Etionamida/metabolismo , Calorimetria , DNA Bacteriano/química , Farmacorresistência Bacteriana , Etionamida/química , Mycobacterium tuberculosis/genética , Espectrometria de Massas por Ionização por Electrospray , TermodinâmicaRESUMO
G-quadruplexes have found increasing potential in applications such as molecular therapeutics, diagnostics, and sensing. As a consequence, small molecules capable of selectively detecting G-quadruplexes have received significant attention in recent literature. Our review here addresses representative advances in the development of luminescent G-quadruplex probes and highlights their potential applications in sensing and imaging.