Thirty Years of the Drug Candidate NAMI-A and the Myths in the Field of Ruthenium Anticancer Compounds: A Personal Perspective

被引:332
作者
Alessio, Enzo [1 ]
机构
[1] Univ Trieste, Dept Chem & Pharmaceut Sci, Via L Giorgieri 1, I-34127 Trieste, Italy
关键词
Medicinal chemistry; Drug discovery; Antitumor agents; Biological activity; Ruthenium; X-RAY-STRUCTURE; IN-VITRO CYTOTOXICITY; HUMAN SERUM-ALBUMIN; CELL LUNG-CANCER; CISPLATIN BINDING-SITES; ANTITUMOR-ACTIVITY; DNA-BINDING; PROTEIN INTERACTIONS; CYCLORUTHENATED COMPOUNDS; HETEROCYCLIC COMPLEXES;
D O I
10.1002/ejic.201600986
中图分类号
O61 [无机化学];
学科分类号
070301 ; 081704 ;
摘要
As anticipated in the title, this contribution is basically divided into two, strictly connected, parts. The first is a personal overview of the ruthenium drug candidate NAMI-A, almost 30 years after its synthesis and the discovery of its unprecedented antimetastatic properties in animal models at nontoxic dosages. The sections relating to the chemical and biological behavior of the complex, and the hypotheses on its mechanism(s) of action, are kept to a minimum, whereas more space is devoted to discussion of the results of the clinical investigations. The second part deals in detail with a number of undemonstrated misconceptions ( or myths) that, over the years, have thrived around NAMI-A and other ruthenium drug candidates, thus negatively affecting the whole field of Ru anticancer drugs.
引用
收藏
页码:1549 / 1560
页数:12
相关论文
共 162 条
[71]   Ruthenium complexes as anticancer agents [J].
Kostova, I .
CURRENT MEDICINAL CHEMISTRY, 2006, 13 (09) :1085-1107
[72]  
Kratz F, 1996, Met Based Drugs, V3, P15, DOI 10.1155/MBD.1996.15
[73]  
KRATZ F, 1994, J BIOL CHEM, V269, P2581
[74]  
Kratz F., 1993, METAL COMPLEXES CANC, P391
[75]   Albumin as a drug carrier: Design of prodrugs, drug conjugates and nanoparticles [J].
Kratz, Felix .
JOURNAL OF CONTROLLED RELEASE, 2008, 132 (03) :171-183
[76]   Phase I/II study with ruthenium compound NAMI-A and gemcitabine in patients with non-small cell lung cancer after first line therapy [J].
Leijen, Suzanne ;
Burgers, Sjaak A. ;
Baas, Paul ;
Pluim, Dick ;
Tibben, Matthijs ;
van Werkhoven, Erik ;
Alessio, Enzo ;
Sava, Gianni ;
Beijnen, Jos H. ;
Schellens, Jan H. M. .
INVESTIGATIONAL NEW DRUGS, 2015, 33 (01) :201-214
[77]   Influence of an anti-metastatic ruthenium(III) prodrug on extracellular protein-protein interactions: studies by bio-layer interferometry [J].
Levina, Aviva ;
Lay, Peter A. .
INORGANIC CHEMISTRY FRONTIERS, 2014, 1 (01) :44-48
[78]   Biotransformations of Anticancer Ruthenium(III) Complexes: An X-Ray Absorption Spectroscopic Study [J].
Levina, Aviva ;
Aitken, Jade B. ;
Gwee, Yee Yen ;
Lim, Zhi Jun ;
Liu, Mimi ;
Singharay, Anannya Mitra ;
Wong, Pok Fai ;
Lay, Peter A. .
CHEMISTRY-A EUROPEAN JOURNAL, 2013, 19 (11) :3609-3619
[79]   Recent developments in ruthenium anticancer drugs [J].
Levina, Aviva ;
Mitra, Anannya ;
Lay, Peter A. .
METALLOMICS, 2009, 1 (06) :458-470
[80]   Synthesis of cycloruthenated compounds as potential anticancer agents [J].
Leyva, Lida ;
Sirlin, Claude ;
Rubio, Laura ;
Franco, Cecilia ;
Le Lagadec, Ronan ;
Spencer, John ;
Bischoff, Pierre ;
Gaiddon, Christian ;
Loeffler, Jean-Philippe ;
Pfeffer, Michel .
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, 2007, (19) :3055-3066