RESUMO
Superoxide anion (O2â¢-) plays a pivotal role in the generation of other reactive oxygen species within the body and is closely linked to epilepsy. Despite this connection, achieving precise imaging of O2â¢- during epilepsy pathology remains a formidable challenge. Herein, we develop an activatable molecular probe, CL-SA, to track the fluctuation of the level of O2â¢- in epilepsy through simultaneous fluorescence imaging and chemiluminescence sensing. The developed probe CL-SA demonstrated its efficacy in imaging of O2â¢- in neuronal cells, showcasing its dual optical imaging capability for O2â¢- in vitro. Furthermore, CL-SA was successfully used to observe aberrantly expressed O2â¢- in a mouse model of epilepsy. Overall, CL-SA provides us with a valuable tool for chemical and biomedical studies of O2â¢-, promoting the investigation of O2â¢- fluctuations in epilepsy, as well as providing a reliable means to explore the diagnosis and therapy of epilepsy.
Assuntos
Sondas Moleculares , Superóxidos , Camundongos , Animais , Humanos , Espécies Reativas de Oxigênio , Células Hep G2 , Imagem Óptica/métodos , Corantes Fluorescentes/químicaRESUMO
Large-scale extraction of the leaves of the Australian rainforest tree Maytenus bilocularis followed by extensive purification studies afforded the targeted and abundant dihydro-ß-agarofuran, bilocularin A, in sufficient quantities (>500 mg) for detailed semi-synthetic chemistry. Eight bilocularin A carbamate analogues were synthesised using a series of commercially available isocyanate reagents in high purity (>95%) and variable yields (9-91%). All previously undescribed analogues were spectroscopically characterised using NMR, UV, IR and MS data. One compound afforded crystalline material and subsequent single crystal X-ray analysis (Cu-Kα) confirmed the chemical structure along with the absolute configuration. All compounds were evaluated for anti-proliferative activity against the human prostate cancer cell line LNCaP; none of the compounds showed significant (>50%) growth inhibition at 20 µM. Compounds were also tested for their ability to inhibit leucine transport in LNCaP cells, and two analogues showed moderate activity with IC50 values of 8.9 and 8.5 µM. This is the first reported synthesis of dihydro-ß-agarofuran carbamate derivatives.
Assuntos
Neoplasias da Próstata , Sesquiterpenos , Austrália , Carbamatos/farmacologia , Humanos , Leucina , Masculino , Estrutura Molecular , Neoplasias da Próstata/tratamento farmacológicoRESUMO
Dynamic covalent polymers-dynamers-are adaptive materials that offer timely variant adaptive macroscopic organization across extended scales. In the current study, imine exchange reactions and fluorescence transfer can occur at the interfaces between various solutions and solid state dynameric films. The fluorescence quenching upon imine formations for designed fluorogen was successfully demonstrated, and this tunable fluorescence was further used to study the re-composition of a solid film. Moreover, the dynamic covalent films also exhibited responsiveness to competing amines and acid/base conditions, both in solutions and solid film-solution interface. This work can provide more insights into interface dynamic chemistry and holds great potential for further applications in optical and biomedical materials.