ADRHYANN JULLYANNE DE SOUSA PORTILHO,CARINNE BORGES DE SOUZA MORAES REGO GOMES,CAROLINE DE FATIMA AQUINO MOREIRA NUNES,CAROLINE DOS SANTOS MOREIRA,DANILO DAMASCENO ROCHA,DAVID RODRIGUES DA ROCHA,FELIP
申请号：
BR102018007385
公开号：
BR102018007385A2
申请日:
2018.04.12
申请国别(地区):
BR
年份:
2019
代理人:
摘要：
The treatment for hematologic malignancies has been facing difficulties, such as resistance and low response to drugs used in the clinic. Resistance mechanisms include membrane transporters (abc family), which contribute to the development of antineoplastic resistance. therefore, the present invention relates to the group of thiocompounds which are 5-hydroxy-2- (p-methylthiecresol) -1,4-naphthoquinone (cnn1), 5-hydroxy-2- (o-methylthiophenol) 1,4-naphthoquinone (cnn3), 5-hydroxy-2- (p-chlorothiophenol) -1,4-naphthoquinone (cnn5), 5-hydroxy-2- (p-methoxythiophenol) -1,4-naphthoquinone (cnn7) and 5-hydroxy-2- (2-furanomethanethiol) -1,4-naphthoquinone (cnn9) as potential antitumor agents and chemoresistance modulators in leukemia. In order to obtain the compounds, the 2-chloro-juglone intermediate was synthesized by disulfide, after purification by liquid chromatography, resulting in thiocompounds. the cytotoxic and chemomodulatory profile of thiocompounds was determined by the alamar blue assay in three leukemic strains: two sensitive (k562 and hl60) and one chemotherapeutic resistant (k562-lucena 1), in addition to the non-neoplastic fibroblast strain (mrc5). The results showed high cytotoxicity in leukemic strains, with higher activity in resistant strains k562-lucena 1, presenting ci 50 below 1 µm. In contrast, thioethers showed low cytotoxic activity in the non-tumor line mrc5, with ci 50 values greater than 8 µm. Therefore, we consider that the thioether group presents reduced toxicity in normal cells and selective chemoresistance modulating activity in leukemia.o tratamento para neoplasias hematológicas vem enfretando dificuldades, como a resistência e a baixa resposta aos fármacos utilizados na clínica. dentre os mecanismos de resistência estão os transportadores de membrana (família abc), que contribuem no desenvolvimento de resistência aos antineoplásicos. sendo assim, a presente invenção refere-se à obtenção do grupo de tiocompostos que são 5-hidroxi-2-(p-m
