Design, Synthesis, and Biological Activity of Marinacarboline Analogues as STAT3 Pathway Inhibitors for Docetaxel-Resistant Triple-Negative Breast Cancer.
J Med Chem
; 66(4): 3106-3133, 2023 02 23.
Article
em En
| MEDLINE
| ID: mdl-36786551
ABSTRACT
Metastatic triple-negative breast cancer (mTNBC) is a fatal type of breast cancer (BC), and signal transducer and activator of transcription 3 (STAT3) has emerged as an effective target for mTNBC. In the present study, compound MC0704 was found to be a novel synthetic STAT3 pathway inhibitor, and its potential antitumor activity was demonstrated using in vitro and in vivo models in docetaxel-resistant TNBC cells. Based on marinacarboline (MC), a series ß-carboline derivatives were synthesized and investigated for their antitumor activities against docetaxel-resistant MDA-MB-231 (MDA-MB-231-DTR) cells. Combining antiproliferation and STAT3 inhibitory activities, MC0704 was selected as the most promising ß-carboline compound. MC0704 effectively impeded the metastatic potential of MDA-MB-231-DTR cells in vitro, and the combination of MC0704 and docetaxel exhibited potent antitumor activities in a xenograft mouse model. These findings suggested that MC0704 can be a lead candidate as a target therapeutic agent for TNBC patients with docetaxel resistance.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias de Mama Triplo Negativas
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article