RESUMO
A series of PROTACs (PROteolysis-TArgeting Chimeras) consisting of bicalutamide analogs and thalidomides were designed, synthesized, and biologically evaluated as novel androgen receptor (AR) degraders. In particular, we found that PROTAC compound 13b could successfully demonstrate a targeted degradation of AR in AR-positive cancer cells and might be a useful chemical probe for the investigation of AR-dependent cancer cells, as well as a potential therapeutic candidate for prostate cancers.
Assuntos
Antagonistas de Androgênios/química , Anilidas/química , Nitrilas/química , Receptores Androgênicos/química , Talidomida/química , Compostos de Tosil/química , Antagonistas de Androgênios/síntese química , Antagonistas de Androgênios/farmacologia , Anilidas/farmacologia , Sítios de Ligação , Linhagem Celular , Técnicas de Química Sintética , Humanos , Modelos Biológicos , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Nitrilas/farmacologia , Ligação Proteica , Proteólise/efeitos dos fármacos , Receptores Androgênicos/metabolismo , Relação Estrutura-Atividade , Talidomida/farmacologia , Compostos de Tosil/farmacologiaRESUMO
In an effort to identify novel anti-inflammatory compounds, a series of flavone derivatives were synthesized and biologically evaluated for their inhibitory effects on the production of nitric oxide (NO) and prostaglandin E2 (PGE2), representative pro-inflammatory mediators, in LPS-induced RAW 264.7 cells. Their structure-activity relationship was also investigated. In particular, we found that compound 3g displayed more potent inhibitory activities on PGE2 production, similar inhibitory activities on NO production and less weak cytotoxicity than luteolin, a natural flavone known as a potent anti-inflammatory agent.