ANSELMO VIEGAS GARCIA, Maria Helena,FERREIRA MORAIS, Tânia Sofia,ANTUNES TOMAZ DINIZ, Ana Isabel,MARUJO MARQUES, Fernanda,FERNANDES MENDES, Filipa
申请号：
IBIB2012/054914
公开号：
WO2013/038395A1
申请日:
2012.09.17
申请国别(地区):
WO
年份:
2013
代理人:
摘要：
The family of ruthenium compounds that is subject of the present patent was found to exhibit great potential as pharmaceutical agents for the treatment of cancer condition. In fact, the present compounds which structure is based on piano stool Μ(η5- ciclopentadienyl ) (M=Ru, Fe) possessing compulsory sigma bonded heteroaromatic ligands to treat tumor and /or metastasis. These compounds displayed very high efficiency in vitro in what concerns their cytotoxicity against a wide range of tumor cells significantly surpassing the activity of the benchmark metallodrug cisplatin currently in clinical use. In addition, we have identified biological targets involved in th mode of action of the ruthenium compounds such as, PARP-1 (a Poly- (adenosine diphosphate (ADP) -ribose) polymerase enzyme) and cell regulatory proteins (cytochrome C and ubiquitin). Although DNA is not the main target of the ruthenium compounds, their interaction with DNA was proved by different approaches. These agents bind to albumin which can provide a vehicle for their transport in the blood stream without loss of activity. Overall this family of compounds encloses a panel of highly promising new anti-tumor ruthenium agents with a large spectrum of activity.La présente invention concerne la famille des composés de ruthénium, qui possèdent un grand potentiel en tant quagents pharmaceutiques dans le traitement des états cancéreux. Les composés selon linvention, qui présentent une structure Μ(η5-ciclopentadiényle)(M = Ru, Fe) en forme de « tabouret de piano » possédant des ligands hétéroaromatiques à liaisons sigma obligatoires, permettent de traiter les tumeurs et/ou les métastases. Lesdits composés présentent une très grande efficacité in vitro en ce qui concerne leur cytotoxicité contre une large gamme de cellules tumorales, surpassant significativement lactivité du cisplatine, le métallo-médicament standard actuellement utilisé cliniquement. En outre, nous avons identifié des cibles biologiques impli
