RESUMEN
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.
Asunto(s)
Neoplasias de la Próstata , Uracil-ADN Glicosidasa , Humanos , Masculino , Uracil-ADN Glicosidasa/química , Oligonucleótidos , Gluconato de Sodio Antimonio , Evaluación Preclínica de Medicamentos , Reposicionamiento de Medicamentos , Detección Precoz del CáncerRESUMEN
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.
Asunto(s)
ADN Bacteriano/metabolismo , Etionamida/metabolismo , Calorimetría , ADN Bacteriano/química , Farmacorresistencia Bacteriana , Etionamida/química , Mycobacterium tuberculosis/genética , Espectrometría de Masa por Ionización de Electrospray , TermodinámicaRESUMEN
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.