RESUMO
In this study, we report the synthesis of a series of chalcone-benzoxaborole hybrid molecules and the evaluation of their anticancer activity. Their anticancer potency and toxicity were tested on three human cancer cell lines and two normal cell lines. The 4-fluoro compound 15 was found to be the most potent compound with an IC50 value of 1.4µM on SKOV3 cells. The 4-iodo compound 18 and 3-methyloxy-4-amino compound 47 showed good potency on SKOV3 cells while exhibiting low toxicity on normal cells. This work extended the application of benzoxaboroles to the field of anticancer research.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Compostos de Boro/química , Compostos de Boro/farmacologia , Chalcona/análogos & derivados , Chalcona/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Descoberta de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias/tratamento farmacológico , Relação Estrutura-AtividadeRESUMO
We report the novel chalcone-benzoxaborole hybrids and their structure-activity relationship against Trypanosoma brucei parasites. The 4-NH(2) derivative 29 and 3-OMe derivative 43 were found to have excellent potency. The synergistic 4-NH(2)-3-OMe compound 49 showed an IC(50) of 0.010 µg/mL and resulted in 100% survival and zero parasitemia in a murine infection model, which represents one of the most potent compounds discovered to date from the benzoxaborole class that inhibit T. brucei growth.
Assuntos
Compostos de Boro/síntese química , Chalconas/síntese química , Tripanossomicidas/síntese química , Trypanosoma brucei brucei/efeitos dos fármacos , Animais , Compostos de Boro/química , Compostos de Boro/farmacologia , Linhagem Celular Tumoral , Chalconas/química , Chalconas/farmacologia , Concentração Inibidora 50 , Camundongos , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade , Tripanossomicidas/química , Tripanossomicidas/farmacologia , Tripanossomíase Africana/tratamento farmacológicoRESUMO
As the best-characterized ubiquitin-like protein (UBL), small ubiquitin-related modifier (SUMO) was found to conjugate with a number of proteins to regulate cellular functions including transcription, signal transduction, and cell cycle. While E1, E2 and E3 ligases are responsible for the forward SUMOylation reaction, SUMO-specific proteases (SENPs) reversibly remove SUMO from the SUMOylated proteins. Recently, SENP1 was found to be a potential therapeutic target for the treatment of prostate cancers, but the design and synthesis of its inhibitors have not been reported. We designed and synthesized a series of benzodiazepine-based SENP1 inhibitors, and they showed inhibitory activity as good as IC(50)=9.2µM (compound 38). The structure-activity relationship was also discussed.
