RESUMEN
A photoredox/copper-catalyzed cascade radical cyclization/phosphorothiolation reaction of N-allylbromoacetamides and P(O)SH compounds has been established. A broad range of novel nonfluorine- or difluoro-substituted 2-pyrrolidinones bearing the C(sp3)-SP(O)(OR)2 moiety can be conveniently constructed in moderate to good yields under mild conditions. Importantly, most of the tested phosphorothiolated 2-pyrrolidinones showed potent inhibitory effects toward both AChE and BChE.
RESUMEN
Herein, the effect of long noncoding RNA forkhead box D1 antisense RNA 1 (FOXD1-AS1) on malignant phenotypes of prostate cancer (PCa) cells was investigated. FOXD1-AS1 presented high expression in PCa cells according to the results of RT-qPCR. As shown by cell counting kit-8 assays, colony formation assays, wound-healing assays, Transwell assays and flow cytometry analyses, silenced FOXD1-AS1 suppressed PCa cell viability, proliferation, migration and invasion and enhanced cell apoptosis. Additionally, FOXD1-AS1 was primarily localised in cytoplasm of PCa cells. RNA immunoprecipitation assays and luciferase reporter assays revealed that FOXD1-AS1 interacted with miR-3167 in PCa cells. MiR-3167 functioned as an anti-oncogene in PCa and miR-3167 overexpression suppressed cell proliferation while promoted cell apoptosis. Moreover, the downstream target of miR-3167 is mRNA YWHAZ. FOXD1-AS1 elevated the expression of YWHAZ by binding with miR-3167. The suppressive effect of miR-3167 on YWHAZ expression was reversed by FOXD1-AS1 overexpression. Furthermore, overexpressed YWHAZ reversed the suppressive effect of FOXD1-AS1 deficiency on malignant behaviours of PCa cells. Overall, FOXD1-AS1 facilitates malignant phenotypes of PCa cells by up-regulating YWHAZ via miR-3167. The study first reveals the molecular mechanism of FOXD1-AS1 in PCa, suggesting that FOXD1-AS1 and its downstream molecules might be prognostic biomarkers before medical treatment.
Asunto(s)
MicroARNs , Neoplasias de la Próstata , ARN Largo no Codificante , Proteínas 14-3-3 , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , MicroARNs/genética , Neoplasias de la Próstata/genética , ARN sin Sentido , ARN Largo no Codificante/genéticaRESUMEN
A photoredox and copper-catalyzed fluoroalkylphosphorothiolation of activated and unactivated alkenes via a radical relay mechanism is reported. By employing fluoroalkyl halides as radical precursors and P(O)SH or P(S)SH compounds as coupling partners, a wide range of ß-monofluoroalkyl-, -difluoroalkyl-, -trifluoromethyl-, or -perfluoroalkyl-substituted S-alkyl phosphorothioates and phosphorodithioates can be easily constructed under mild conditions with good functional group tolerance. Furthermore, this modular reaction system can be successfully applied to late-stage functionalization of bioactive molecules.
