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1 2010

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Kompleksy rutenu w terapii antynowotworowej

Richert M., Budzisz E.

Wiadomości Chemiczne

2010

[Z] 64, 5-6

357-387

Chemotherapy is a major cancer treatment besides surgery and ratiotherapy. One of the most popular chemotherapeutic drugs that are currently in use are platinum compounds. Despite the success of cisplatin and other platinum-based anticancer compounds in cancer therapy [1, 2] there is still a need for new improved drugs with lower toxicity against healthy cells, better activity against tumor, less side effects, and without problems with drug resistance in primary and metastatic cancers [3, 4]. One of the most promising metals in the cancer treatment is ruthenium [6, 21,22]. Ruthenium complexes appear generally less toxic than platinum-based complexes and show activity in cisplatin-resistant cells or in cells where cisplatin is inactive. In spite of development of promising ruthenium(II) compounds, in particular organometallics [50, 51], only ruthenium(III) complexes like (H2Im)[trans-Ru(DMSO)Cl4(HIm)], (NAMI-A) [62] (Ryc. 7a) and (HInd)[Ru(III)Cl4(Ind)2], (KP1019) [23] (Ryc. 7b) gain the phase II of clinical trials. The complex NAMI-A showed marked efficacy against metastases whereas KP1019 was highly active against a colorectal tumor cells both in vivo and in vitro. Moreover the second compound is completely devoid of side effects and drug induced lethality at therapeutically relevant doses. Its therapeutic index is better than that of (HIm)[Ru(III)Cl4(Im)2]. The complex (HInd)[Ru(III)Cl4(Ind)2] has been shown to be efficiently taken up into the cells probably via interaction with transferrin. It induces apoptosis, but the cellular mechanisms of the apoptosis induction are still largely unknown [30]. Non-cross-resistance in cisplatin-resistant cancer cells and reduced toxicity, which is in part due to the ability of ruthenium complexes to mimic the binding of iron to molecules of biological significance, exploiting the mechanisms that the body has evolved for non-toxic transport of iron, is a particularly attractive feature of ruthenium complexes [16]. In addition, some chemical properties, such as rate of ligand exchange, range of accessible oxidation states, and ability of ruthenium to mimic iron in binding to certain biological molecules make these compounds well suited for medicinal applications as an alternative to platinum antitumor drugs in the treatment of cancer cells resistant to cisplatin and its analogues justifying further development of this novel and interesting group of metal complexes [30].