双核铂-双膦酸盐配合物的合成、表征及其作为骨肿瘤局部治疗前药的细胞毒性。
Synthesis, characterization, and cytotoxicity of dinuclear platinum-bisphosphonate complexes to be used as prodrugs in the local treatment of bone tumours.
机构信息
Dipartimento Farmaco-Chimico, Università degli Studi di Bari A. Moro, Via E. Orabona 4, 70125, Bari, Italy.
出版信息
Dalton Trans. 2009 Dec 28(48):10904-13. doi: 10.1039/b919721d. Epub 2009 Nov 16.
For over 30 years cisplatin has been one of the most active antitumour agents in clinical use, nevertheless research for overcoming cisplatin toxicity and resistance or for improving its efficacy has never ceased. In this context we have recently proposed dinuclear Pt complexes with bridging geminal bisphosphonates as novel Pt-prodrugs with potential activity at the bone surface after embedment in inorganic matrices and implantation at the tumour site. In the present paper we report the synthesis and full characterization of four new platinum complexes having a dinuclear structure with a bisphosphonate (2-ammonium-1-hydroxyethane-1,1-diyl-bisphosphonate or 3-ammonium-1-hydroxypropane-1,1-diyl-bisphosphonate, AHBP-H and PAM-H, respectively) acting as a bridging ligand between two platinum moieties (cis-Pt(NH(3))(2), directly related to cisplatin, and Pt(cis-1,4-DACH), known to be able to overcome the cisplatin resistance). Moreover, as a preliminary investigation, the in vitro cytotoxicity of the new complexes has been evaluated on a panel of 13 human tumour cell lines including cisplatin- and multidrug-resistant sublines.
30 多年来,顺铂一直是临床应用中最有效的抗肿瘤药物之一,然而,为了克服顺铂的毒性和耐药性或提高其疗效,研究从未停止过。在这方面,我们最近提出了具有桥联双膦酸盐的双核铂配合物作为新型铂前药,在无机基质中嵌入和在肿瘤部位植入后具有潜在的骨表面活性。在本文中,我们报告了四个具有双核结构的新型铂配合物的合成和全表征,该结构具有双膦酸盐(2-氨-1-羟乙叉-1,1-二膦酸盐或 3-氨-1-羟丙烷-1,1-二膦酸盐,分别为 AHBP-H 和 PAM-H)作为两个铂部分(顺式-[Pt(NH3)(2)](2+)之间的桥联配体,直接与顺铂有关,[Pt(顺式-1,4-DACH)](2+),已知能够克服顺铂耐药性)。此外,作为初步研究,对包括顺铂和多药耐药亚系在内的 13 个人类肿瘤细胞系进行了新配合物的体外细胞毒性评估。